A 2016 Cochrane review found no evidence that melatonin helped sleep problems in people with moderate to severe dementia due to Alzheimer's disease. A 2019 review found that while melatonin may improve sleep in minimal cognitive impairment, after the onset of Alzheimer's it has little to no effect. Melatonin may, however, help with sundowning.
Dementia
Melatonin
Melatonin | Dementia
No. No No evidence is found No.
the primary high energy molecule in human metabolism is
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Adenosine triphosphate (ATP)
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what is catabolism?
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It is the set of metabolic processes that breaks down large molecules.
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which hormones are related to it?
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Cortisol, glucagon, adrenaline, cytokines, orexin and melatonin.
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what is the emotional response due to the third one?
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Fear.
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how does the first hormone related to metabolism of glucose?
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Cortisol stimulates the synthesis of 'new' glucose from non-carbohydrate sources; this is known as gluconeogenesis..
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is process resisted by insulin?
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Yes.
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when was this substance which resists the process discovered?
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1921.
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can it be extracted?
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Yes.
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from where?
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Pancreas.
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can we find in plants the last hormone in the list of hormones mentioned above?
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Yes.
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is it responsible for any memory related disease?
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A 2016 Cochrane review found no evidence that melatonin helped sleep problems in people with moderate to severe dementia due to Alzheimer's disease. A 2019 review found that while melatonin may improve sleep in minimal cognitive impairment, after the onset of Alzheimer's it has little to no effect. Melatonin may, however, help with sundowning.
Melatonin | Dementia
The circadian rhythm taking hold is responsible for the feeling of fatigue. Our body naturally starts to shut down, around the time that the sun starts to take its dip into the horizon. The primary chemical for this happening is melatonin, so it would seem natural to wonder if melatonin has some effect on learning and memory formation as well. Every animal that sleeps also exhibits some bodily concentration of melatonin. When studying the effects of sleepiness on fish, it was found that any significant amount of melatonin causes a "dramatic decrease" in learning and memory formation. This study was performed at night under bright lights, to inhibit the release of natural amounts of melatonin and learning behaviors were conducted.
Metaplasticity | What else may be involved
Melatonin is discharged by the Pineal Gland as a neurohormone. Melatonin is a central hormone in the treatment of patients with Alzheimer’s disease as it adjusts sleep patterns that are abnormal, which occurs in over forty five percent of patients. Melatonin affects type 3 diabetes by reducing harm caused by beta amyloid, regulating hyperglycaemia and insulin resistance in patients with diabetes and stopping blood brain barrier disruption caused by hyperglycaemia. Through these processes, melatonin has been shown to lessen the progression of type 3 diabetes.
Type 3 diabetes | Melatonin administration
This increase in melatonin reduces the ability to learn and facilitate new memories. The ability for melatonin to suppress memory formation is very significant, however. The melatonin would work in conjunction with the LTD during slow oscillations during sleep, to keep individuals from potentiating unwanted, or unneeded, information from their day.
Metaplasticity | What else may be involved
Plants lack a specialized organ devoted to memory retention, and so plant memory has been a controversial topic in recent years. New advances in the field have identified the presence of neurotransmitters in plants, adding to the hypothesis that plants are capable of remembering. Action potentials, a physiological response characteristic of neurons, have been shown to have an influence on plants as well, including in wound responses and photosynthesis. In addition to these homologous features of memory systems in both plants and animals, plants have also been observed to encode, store and retrieve basic short-term memories. One of the most well-studied plants to show rudimentary memory is the Venus flytrap.
Memory | In plants
The combination of these four mechanisms of plant memory are proposed to work together to form different functions of memory in a plant. The overall proposed mechanism of this memory is a signal or environmental cues lead to a signal (chemical concentration, calcium waves, electrical, small RNAs, or phytohormones), and this eventually leads to the activation or deactivation of memory associated genes (store and recall, epigenetics, habituation, or circadian rhythms). The protein products of these genes then go on to produce actions based on the memory of the initial stimuli. The production and actions of these proteins to a past stimuli is the core of observable plant memory in action.
Plant memory | Summary
To further distinguish age-related memory loss from Alzheimer's disease (AD), a subregion of the hippocampal formation called the dentate gyrus (DG) was further studied, since it is thought to be targeted by aging. Human postmortem tissue was collected from both DG and entorhinal cortex (EC). Entorhinal cortex is a neighboring subregion unaffected by aging and known to be implicated in age-related memory loss. After normalizing the expression of EC, 17 genes were manifested due to age-related changes in the DG. Mice were used as the experimental subjects to test whether the decline of RbAp48 was also related to age-related memory loss.
Deficiency of RbAp48 protein and memory loss | Experimental process
Current Research indicates that procedural memory problems in Alzheimer's may be caused by changes in enzyme activity in memory-integrating brain regions such as the hippocampus. The specific enzyme linked to these changes is called acetylcholinesterase (AchE) which may be affected by a genetic predisposition in an immune-system brain receptor called the histamine H1 receptor. The same current scientific information also looks at how dopamine, serotonin and acetylcholine neurotransmitter levels vary in the cerebellum of patients that have this disease. Modern findings advance the idea that the histamine system may be responsible for the cognitive deficits found in Alzheimer's and for the potential procedural memory problems that may develop as a result of the psychopathology.
Procedural memory | Alzheimer's disease and dementia
Age-related memory loss is believed to originate in the dentate gyrus, whereas Alzheimer's is believed to originate in the entorhinal cortex.
Memory and aging | Mechanism research
Leukotrienes are found to play an important role in the later stages of Alzheimer's disease and related dementias in studies with animals. In tau transgenic mice, which develop tau pathology, "zileuton, a drug that inhibits leukotriene formation by blocking the 5-lipoxygenase enzyme" was found to reverse memory loss.
Leukotriene | Leukotrienes in dementia
Melatonin was originally discovered by Aaron Lerner, a Yale dermatologist, and colleagues, who had hoped it could be used to treat vitiligo. Although melatonin did not prove to be relevant to dermatology treatments, it was quickly confirmed to be secreted by the pineal gland to affect the brain. Further research found that circadian melatonin rhythms persisted under constant darkness, which suggested that light alone is not responsible for the cycle of melatonin secretion. Rather, endogenous melatonin serves to internalize light cues, making melatonin responsible for modulating neuroendocrine functions. The suprachiasmatic nucleus, or SCN, is a small region within the anterior hypothalamus of the brain that is responsible for orienting the organism’s internal measurement of time to external time cues like daylight.
Chronobiotic | History
Until its identification in plants in 1987, melatonin was for decades thought to be primarily an animal neurohormone. When melatonin was identified in coffee extracts in the 1970s, it was believed to be a byproduct of the extraction process. Subsequently, however, melatonin has been found in all plants that have been investigated. It is present in all the different parts of plants, including leaves, stems, roots, fruits, and seeds, in varying proportions. Melatonin concentrations differ not only among plant species, but also between varieties of the same species depending on the agronomic growing conditions, varying from picograms to several micrograms per gram.
Melatonin | Plants
The hippocampus is a brain region which has many interconnected subregions, with each region having its own distinct neuron populations playing an important role in encoding memory. Many studies showed that Alzheimer's disease (AD) ameliorates memory by first acting on the entorhinal cortex (EC) which is the region providing the main input conduit from the external sensors to the hippocampus. Scientists initially identified memory loss associated with aging as an early manifestation of Alzheimer's; however, more recent evidence suggests that a distinct process affects the dentate gyrus (DG), which is a subregion of the hippocampus, and causes memory deterioration. The hippocampal formation is made up of many interconnected subregions and plays a vital role in retaining memory.
Deficiency of RbAp48 protein and memory loss | Mechanism
Alzheimer's disease is the most common neurodegenerative disease and is the most common form of dementia in the elderly. The disorder is characterized by progressive loss of memory and various cognitive functions. It is hypothesized that the deposition of amyloid-β peptide (40-42 amino acid residues) in the brain is integral in the incidence of Alzheimer's disease. Accumulation is purported to block hippocampal long-term potentiation. It is also possible that a receptor for amyloid-β oligomers could be a prion protein.
Molecular neuroscience | Alzheimer's disease
The physiology of plant memory is documented in many studies and is understood to have four main physiological mechanisms that work together in synchrony to provide the plant with basic memory functions, and are thought to be precursors to advanced memory functions found in animals. These four mechanisms are the storing and recalling, habituation, gene priming or epigenetics, and the biological clock.
Plant memory | Physiology
This finding is in agreement with an earlier study showing the presence of Reelin associated with amyloid plaques in a transgenic AD mouse model. A large genetic study of 2008 showed that RELN gene variation is associated with an increased risk of Alzheimer's disease in women. The number of reelin-producing Cajal-Retzius cells is significantly decreased in the first cortical layer of patients. Reelin has been shown to interact with amyloid precursor protein, and, according to one in-vitro study, is able to counteract the Aβ-induced dampening of NMDA-receptor activity. This is modulated by ApoE isoforms, which selectively alter the recycling of ApoER2 as well as AMPA and NMDA receptors.
Reelin | Alzheimer's disease
Also, BDNF is important for the persistence of long-term memories. The long-term stabilization of synaptic changes is also determined by a parallel increase of pre- and postsynaptic structures such as axonal bouton, dendritic spine and postsynaptic density. On the molecular level, an increase of the postsynaptic scaffolding proteins PSD-95 and HOMER1c has been shown to correlate with the stabilization of synaptic enlargement. The cAMP response element-binding protein (CREB) is a transcription factor which is believed to be important in consolidating short-term to long-term memories, and which is believed to be downregulated in Alzheimer's disease.
Memory | Genetic underpinnings
Claims have been made of a sugar–Alzheimer's disease connection, but there is inconclusive evidence that cognitive decline is related to dietary fructose or overall energy intake.
Sugar | Alzheimer's disease
A second hypothesis has been generated based on data that suggest GAL is involved in protecting the hippocampus from excitotoxic damage and the neurons in the cholinergic basal forebrain from amyloid toxicity.
Galanin | Alzheimer's disease
Heterozygous mutation of the GRN gene leading to progranulin haploinsufficiency causes Frontotemporal Dementia. These mutations include frameshift, splice site, nonsense signal peptide, Kozak sequence disruptions and missense mutations, which result in either nonsense-mediated decay or the production of non-functional protein. Patients with GRN caused FTD (GRN-FTD) exhibit asymmetric brain atrophy, although age of onset, disease progression and clinical symptoms vary, suggesting that other genetic or environmental factors may be involved in disease expression. Pathological indicators include cytosolic ubiquitin deposits enriched in hyperphosphorylated TAR DNA Binding Protein (TDP-43), autophagy-related protein aggregates, ubiquitin-binding protein p62, lentiform intranuclear inclusions, dystrophic neurites and inflammation.
Granulin | Frontotemporal dementia
Study of the genetics of human memory is in its infancy though many genes have been investigated for their association to memory in humans and non-human animals. A notable initial success was the association of APOE with memory dysfunction in Alzheimer's disease. The search for genes associated with normally varying memory continues. One of the first candidates for normal variation in memory is the protein "KIBRA," which appears to be associated with the rate at which material is forgotten over a delay period. There has been some evidence that memories are stored in the nucleus of neurons.
Memory | Genetics
In contrast to the dose-dependent enhancing effects of glucocorticoids on memory consolidation, these stress hormones have been shown to inhibit the retrieval of already stored information. Long-term exposure to glucocorticoid medications, such as asthma and anti-inflammatory medication, has been shown to create deficits in memory and attention both during and, to a lesser extent, after treatment, a condition known as "steroid dementia".
Glucocorticoid | Arousal and cognition
One receptor for A oligomers may be the prion protein, the same protein that has been linked to mad cow disease and the related human condition, Creutzfeldt–Jakob disease, thus potentially linking the underlying mechanism of these neurodegenerative disorders with that of Alzheimer's disease. In 2009, this hypothesis was updated, suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The hypothesis holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by ageing-related processes in later life to cause the neuronal withering of Alzheimer's disease.
Alzheimer's disease | Amyloid hypothesis
Normal aging, although not responsible for causing memory disorders, is associated with a decline in cognitive and neural systems including memory (long-term and working memory). Many factors such as genetics and neural degeneration have a part in causing memory disorders. In order to diagnose Alzheimer's disease and dementia early, researchers are trying to find biological markers that can predict these diseases in younger adults. One such marker is a beta-amyloid deposit which is a protein that deposits on the brain as we age. Although 20-33% of healthy elderly adults have these deposits, they are increased in elderly with diagnosed Alzheimer's disease and dementia.
Memory disorder | Aging
In vertebrates, melatonin is produced in darkness, thus usually at night, by the pineal gland, a small endocrine gland located in the center of the brain but outside the blood–brain barrier. Light/dark information reaches the suprachiasmatic nuclei from retinal photosensitive ganglion cells of the eyes rather than the melatonin signal (as was once postulated). Known as "the hormone of darkness", the onset of melatonin at dusk promotes activity in nocturnal (night-active) animals and sleep in diurnal ones including humans. Many animals use the variation in duration of melatonin production each day as a seasonal clock. In animals including humans, the profile of melatonin synthesis and secretion is affected by the variable duration of night in summer as compared to winter.
Melatonin | Other animals
Alzheimer’s is a neurodegenerative disease involving progressive memory loss and other declines in brain function. One common cause of familial Alzheimer’s is mutation in the "PSEN1" gene. This gene encodes a protein that cleaves certain intracellular peptides which, once free in the cytoplasm, promote CBPdegradation. Mutations in "PSEN1" decrease its production or ability to cleave proteins. This derepresses the CBP proteins, and allows them to perform their function of upregulating transcription of their target genes.
Derepression | <a href="Familial%20Alzheimer%27s%20Disease">Familial Alzheimer’s disease</a>
It showed an increased genetic susceptibility to more severe dementia with Alzheimer's disease than without the genetic marker.
Memory disorder | Aging
DEMENTIA: Drugs/depression Elderly
List of medical mnemonics | Dementia: reversible dementia causes
Alzheimer's disease accounts for 60 to 70 percent of cases of dementias. The brains of Alzheimer's patients have an abundance of plaques and tangles which begin in areas involved in memory, spreading to other areas, and eventually affecting most of the brain. Vascular dementia is often considered the second-most common form of dementia and is the reduction of blood flow to parts of the brain most often caused by many very small strokes that have an accumulative effect on cognitive abilities including memory.
Retrospective memory | Alzheimer's disease (AD) and vascular dementia (VaD)
Many neurodegenerative diseases can cause memory loss. Some of the most prevalent (and, as a consequence, most intensely researched) include Alzheimer's disease, dementia, Huntington's disease, multiple sclerosis, and Parkinson's disease. None act specifically on memory; instead, memory loss is often a casualty of generalized neuronal deterioration. Currently, these illnesses are irreversible, but research into stem cells, psychopharmacology, and genetic engineering holds much promise. Those with Alzheimer's disease generally display symptoms such as getting momentarily lost on familiar routes, placing possessions in inappropriate locations and distortions of existing memories or completely forgetting memories. Researchers have often used the Deese–Roediger–McDermott paradigm (DRM) to study the effects of Alzheimer's disease on memory.
Long-term memory | Neurodegenerative diseases
Genetic variation in ERβ is both sex and age dependent and ERβ polymorphism can lead to accelerated brain aging, cognitive impairment, and development of AD pathology. Similar to CVD, post-menopausal women have an increased risk of developing Alzheimer's disease (AD) due to a loss of estrogen, which affects proper aging of the hippocampus, neural survival and regeneration, and amyloid metabolism. ERβ mRNA is highly expressed in hippocampal formation, an area of the brain that is associated with memory. This expression contributes to increased neuronal survival and helps protect against neurodegenerative diseases such as AD. The pathology of AD is also associated with accumulation of amyloid beta peptide (Aβ).
Estrogen receptor beta | Alzheimer's disease
The most common treatment is hormone replacement therapy or estrogen therapy. Women using hormone therapy for at least two years have increased blood flow to the hippocampus and temporal lobe as compared to those who did not undergo therapy. These areas of the brain are key to memory. Also, women who do not undergo therapy have been found to have less metabolic activity in the posterior cingulate cortex, while those with estrogen therapy did not show a significant metabolic change. This is important as declines in cerebral metabolism occur in the early stages of Alzheimer's, as mentioned in "Causes". Women who had their uterus and ovaries removed for medical reasons and lost their gonadal hormones showed a decrease in short-term verbal (hippocampus) and working memories (pre-frontal cortex), yet with estrogen therapy the memory loss was prevented.
Postmenopausal confusion | Cognition
One hypothesis that explains how this occurs is by electrical signalling in plants. When one trap hair (mechanoreceptor) is triggered, a sub-threshold potential is reached. When two trap hairs are triggered, threshold is reached and generates an action potential to close the traps.
Plant cognition | Plant memory
The storage and recall method of memory occurs when a plant, in response to a stimuli, reduces or increases the concentration of a chemical in certain tissues, and maintains this concentration for a certain period of time. The plant then uses this concentration of chemical as a signal for a recall response. Stimuli known to create a store and recall responses like this are touch, damage, temperature, and even electromagnetic radiation. It is suspected that Ca2+ signalling plays a key role in this form of plant memory. A proposed mechanism of this is that the presence or absence of Ca acts as a long term on/off switch for cellular processes in response to stimuli for storing genes.
Plant memory | Storage and recall
While a proper concentration of Aβ in the brain is important for healthy functioning, too much can lead to cognitive impairment. Thus, ERβ helps control Aβ levels by maintaining the protein it is derived from, β-amyloid precursor protein. ERβ helps by up-regulating insulin-degrading enzyme (IDE), which leads to β-amyloid degradation when accumulation levels begin to rise. However, in AD, lack of ERβ causes a decrease in this degradation and an increase in plaque build-up. ERβ also plays a role in regulating APOE, a risk factor for AD that redistributes lipids across cells. APOE expression in the hippocampus is specifically regulated by 17βE2, affecting learning and memory in individuals afflicted with AD.
Estrogen receptor beta | Alzheimer's disease
Alzheimer's is a neuropathological disease that is hypothesized to result from the loss of dendritic spines and/or deformation of these spines in the patient's frontal and temporal cortices. Researchers have tied the disease to a decrease in the expression of drebrin, a protein thought to play a role in long-term potentiation, meaning the neurons would lose plasticity and have trouble forming new connections. This malfunction presents itself in the form of helical filaments that tangle together in the neuropil. This same phenomenon seems to occur in the elderly as well.
Neuropil | Alzheimer's disease
Some places of noted degradation include the median raphe nuclei, the noradrenergic parts of the locus coeruleus, and the cholinergic neurons in the parabrachial area and pedunculopontine nuclei of the tegmentum.
Hallucination | Parkinson's disease and Lewy body dementia
A decrease of RbAp48 in the dentate gyrus (DG) of the hippocampus in the brain is suspected to be a main cause of memory loss in normal aging. An age related decrease in RbAp48 is observed in the DG from human post-mortem tissue and also in mice. Furthermore, a gene knockin of a dominant negative form of RbAp48 of causes memory deficits in young mice similar to that observed in older mice. Finally lentiviral gene transfer to increase the expression of RbAp48 in the brain reverses memory deficits in older mice. RBBP4 works at least in part through the PKA-CREB1-CPB pathway.
RBBP4 | Clinical significance
A deficiency of the RbAp48 protein has been associated with age-related memory loss. In 2010, experiments that have tested for the significance of under-performance of memory for an older adult group as compared to a young adult group, hypothesized that the deficit in associate memory due to age can be linked with a physical deficit. This deficit can be explained by the inefficient processing in the medial-temporal regions. This region is important in episodic memory, which is one of the two types of long-term human memory, and it contains the hippocampi, which are crucial in creating memorial association between items.
Memory and aging | Mechanism research
This study demonstrates that there is a nocturnal peak production of melatonin in "E. brasiliensis" and that melatonin is the result of a biological clock, not light, though it can be a stimulus.
Echinaster | Research
By suppressing "dunce" through mutagenesis, the "amnesiac" gene plays a role in reproduction of "Drosophila" because "dunce" is the sterility gene. This molecule has similar peptides to pituitary adenylyl cyclase-activating peptide (PACAP) and growth hormone-releasing hormone (GHRH). The biological role of "amnesiac" gene is activating the adenyl cyclase second messenger pathway (cAMP) involved in its memory retrieval through these two peptides. The sensory and motor capabilities of "amnesiac" are normal, but it is memory retrieval that is affected, not storage. The "amnesiac" gene is directly involved in development of memory retrieval in the brain along with alcohol sensitivity patterning.
Amnesiac gene | Biological role
Several genes, proteins and enzymes have been extensively researched for their association with memory. Long-term memory, unlike short-term memory, is dependent upon the synthesis of new proteins. This occurs within the cellular body, and concerns the particular transmitters, receptors, and new synapse pathways that reinforce the communicative strength between neurons. The production of new proteins devoted to synapse reinforcement is triggered after the release of certain signaling substances (such as calcium within hippocampal neurons) in the cell. In the case of hippocampal cells, this release is dependent upon the expulsion of magnesium (a binding molecule) that is expelled after significant and repetitive synaptic signaling.
Memory | Genetic underpinnings
Up to this point, studies have not agreed as to whether or not these processes are dependent on corticosterone or what even happens based on corticosterone in these processes and how memory is ultimately affected.
Corticosterone | Effect on memory
Plaques are dense, mostly insoluble deposits of beta-amyloid peptide and cellular material outside and around neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves. Although many older individuals develop some plaques and tangles as a consequence of ageing, the brains of people with AD have a greater number of them in specific brain regions such as the temporal lobe. Lewy bodies are not rare in the brains of people with AD.
Alzheimer's disease | Neuropathology
Similar to human action potentials, they hypothesized that the first stimulus led to an increase of calcium. These levels are retained, allowing memory. If the second stimulus takes too long to occur, then the combined calcium levels will not surpass the threshold required to trigger the trap shutting. In this way, the memory would be lost. If the second stimulus occurred quickly enough, then the calcium levels would breach the threshold and trigger the trap to close. This demonstrated delayed response to the stimulus.The maintenance of the initial trigger through calcium levels is an example of a mechanism by which short-term memory can occur in plants.
Plant memory | History
In 1994, Reppert cloned human and sheep Mel melatonin receptor, the first in a family of GPCRs that bind the pineal hormone melatonin, and localized its expression in the mammalian brain to the SCN and the hypophyseal pars tuberalis. Mel is believed to be responsible for the circadian effects of melatonin and the reproductive actions in seasonal breeding mammals. In 1995, Reppert cloned and characterized the Mel melatonin receptor. He and colleagues found that the receptor was predominantly expressed in the retina, where it is believed to modify light-dependent retinal functions. They identified outbred populations of Siberian hamsters that lacked functional Mel but maintained circadian and reproductive responses to melatonin; these data indicate that Mel is not necessary for the circadian and reproductive actions of melatonin, which instead depend on Mel.
Steven M. Reppert | Mammalian melatonin receptors
The DRM paradigm presents a list of words such as doze, pillow, bed, dream, nap, etc., with a theme word that is not presented. In this case, the theme word would have been sleep. Alzheimer's disease patients are more likely to recall the theme word as being part of the original list than healthy adults. There is a possible link between longer encoding time and increased false memory in LTM. The patients end up relying on the gist of information instead of the specific words themselves. Alzheimer's leads to an uncontrolled inflammatory response brought on by extensive amyloid deposition in the brain, which leads to cell death in the brain.
Long-term memory | Neurodegenerative diseases
Estrogen may also help in the prevention of dementia but cannot help when dementia is already present and when cognitive function is already impaired. It increases cerebral blood flow and is an anti-inflammatory agent, enhancing activity at the neuronal synapses in the brain. It may also help to increase brain activation in regions that are affected by dementia which is mainly the hippocampus region. Recent evidence on the effects of estrogen do not allow for an unambiguous recommendation for estrogen supplementation and they indicate that the timing of estrogen supplementation may be important, with early postmenopausal use being preferable over its use later in life.
Prevention of dementia | Steroid hormones
Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, Sheline YI, Klunk WE, Mathis CA, Morris JC, Mintun MA (2005) Molecular, structural, and functional characterization of Alzheimer’s disease: Evidence for a relationship between default activity, amyloid, and memory. J Neurosci: 7709-17. Buckner RL, Carroll DC (2007) Self-projection and the brain. Trends Cognit Sci, 11: 49-57. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: Anatomy, function, and relevance to disease. Ann New York Acad Sci, 1124: 1-38.
Randy Buckner | Selected publications
Since the disease was first described by Alois Alzheimer in 1906, the only certain way to determine if a person indeed had the disease was to perform a biopsy on the patient's brain to find distinctive spots on the brain that show the buildup of amyloid plaque. Doctors must diagnose the disease in patients with memory loss and dementia based on symptoms, and as many as 20% of patients diagnosed with the disease are found after examination of the brain following death not to have had the condition. Other diagnostic tools, such as analysis of cerebrospinal fluid, magnetic resonance imaging scans looking for brain shrinkage and PET scans looking at how glucose was used in the brain, had all been unreliable.
Florbetapir (18F) | Development
Alzheimer's disease (AD) is a progressive, degenerative and fatal brain disease, in which cell to cell connections in the brain are lost. Alzheimer's disease is the most common form of dementia. Globally approximately 1–5% of the population is affected by Alzheimer's disease. Women are disproportionately the victims of Alzheimer's disease, with evidence suggesting that women with AD display more severe cognitive impairment relative to age-matched males with AD, as well as a more rapid rate of cognitive decline.
Memory disorder | Alzheimer's disease
Memory-enhancement of emotional events depend on noradrenergic transmission. In 2007, de Quervain has shown that a deletion variant of the alpha2b-adrenoceptor is related to enhanced emotional memory in Europeans and Africans. Furthermore, using genome mapping, de Quervain has found that the receptor HRH1 can be targeted with drugs to hamper memory. When HRH1 was targeted with drugs, a single administration of the drug decreased recall of aversive memories but had no effect on neutral or positive memories. This approach can be used to develop medications to enhance memory recall or reduce the retrieval traumatic memories in PTSD patients. de Quervain has also found a genetic link between HSD11B1 and the risk for developing Alzheimer's.
Dominique de Quervain | Genetics of memory
Memory tends to begin to fade as when enter and go through adulthood. Ane-Victoria Idland et al., investigated the biological factors that begin to form in a person’s older life and examined biological markers that could help explain the decrease in memory. They focused on beta amyloid 1–42 (Aβ42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL), and their findings suggest that tauopathy and FABP3 tended to be associated with the most memory decline. As individuals age, the hippocampus appears to begin to lose its ability to make connections to life events and memory.
Memory development | Adults
In 1994 his lab published work showing that melatonin is a hormone, secreted at night-time, needed for the induction & maintenance of normal sleep.
Richard Wurtman | Notable findings
Some of Axelrod's later research focused on the pineal gland. He and his colleagues showed that the hormone melatonin is generated from tryptophan, as is the neurotransmitter serotonin. The rates of synthesis and release follows the body's circadian rhythm driven by the suprachiasmatic nucleus within the hypothalamus. Axelrod and colleagues went on to show that melatonin had wide-ranging effects throughout the central nervous system, allowing the pineal gland to function as a biological clock. He was elected a Fellow of the American Academy of Arts and Sciences in 1971. He continued to work at the National Institute of Mental Health at the NIH until his death in 2004.
Julius Axelrod | Pineal gland research
Patients with the heterozygote mutation exhibit a reduction of 70-80% serum progranulin levels when compared to controls. Reprogrammed stem cells restore GRN mRNA levels to 50%, further suggesting that some other genetic or environmental factor is involved in regulating FTD disease expression. Mice exhibit reduced autophagic flux and autophagy-dependent clearance. Human FTLD-GRN derived fibroblasts show decrease lysosomal protease activity and lymphoblasts containing neuronal ceroid lipofuscinosis-like storage material. FTLD-GRN IPSC cortical Neurons have enlarged vesicles, lipofuscin accumulation and cathepsin D deficiency.
Granulin | Frontotemporal dementia
It is thought that with the development of plaques and tangles associated with Alzheimer's disease there might be a disruption within the suprachiasmatic nucleus (SCN). The SCN is associated with regulating sleep patterns by maintaining circadian rhythms, which are strongly associated with external light and dark cues. A disruption within the suprachiasmatic nucleus would seem to be an area that could cause the types of confusion that are seen in sundowning. However, finding evidence for this is difficult, as an autopsy is needed to analyse this disruption properly. By the time an Alzheimer's patient has died, they have usually surpassed the level of brain damage (and associated dementia) that would be associated with sundowning.
Sundowning | Disturbances in circadian rhythms
The pineal gland secretes the hormone melatonin "directly into the systemic circulation", thus melatonin is not affected by the blood-brain barrier.
Blood–brain barrier | Structure
"Dementia" is a term referring to neurodegenerative disorders characterized by a loss of memory and such brain functions executive functioning. Included under this umbrella term is Alzheimer's disease. Alzheimer's disease is characterized by the loss of cortical functions like language and motor skills. Patients with Alzheimer's disease exhibit an extreme shrinkage of the cerebral cortex and hippocampus with an enlargement of the ventricles. In several recent studies, higher vitamin D levels have been associated with lower risks of developing Alzheimer's disease. Alzheimer's disease is associated with a decrease in vitamin D receptors in the "Cornu Ammonius" areas (CA 1& 2) of the hippocampus.
Vitamin D and neurology | Dementia: Alzheimer's disease
An inflammatory hypothesis is that AD is caused due to a self-perpetuating progressive inflammation in the brain culminating in neurodegeneration. A possible role of chronic periodontal infection and the gut microbiota has been suggested. A neurovascular hypothesis has been proposed which states that poor functioning of the blood–brain barrier may be involved. Spirochete infections have also been linked to dementia. The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in AD, though it remains unclear whether this is produced by or causes the changes in proteins. These ions affect and are affected by tau, APP, and APOE, and their dysregulation may cause oxidative stress that may contribute to the pathology.
Alzheimer's disease | Other hypotheses
Even though this is not what many would consider human memory, the fundamentals of what have occurred are the same. The storage of the input, whether it be a smell to a human or a touch to a plant, is fundamentally the same in terms of the previously discussed definition of basic memory. As this field of study moves forward, some new questions regarding plants’ abilities to retain information have arisen. One such question surrounds the length of plant memory. While evidence supported short term retention of signals, some scientists wanted to see if plants could retain information for longer periods of time similar to the way that humans can.
Plant memory | History
Amyloid plaques formed by amyloid-β (Aβ) deposition and neurofibrillary tangles formed by tau protein phosphorylation are dominant physiological features of Alzheimer's disease. Amyloid precursor protein (APP) proteolysis is fundamental for production of Aβ peptides implicated in AD pathology. By using a cell line that contains high levels of estrogen receptors, scientists found that treatment with physiological concentrations of 17 beta-estradiol is associated with accumulation in the conditioned medium of an amino-terminal cleavage product of APP (soluble APP or protease nexin-2), indicative of non-amyloidogenic processing.
Estrogen and neurodegenerative diseases | Estrogen and Alzheimer's disease
While extracellular amyloid beta (Aβ) plaques, neurofibrillary tangles (NFT), inflammation in the form of reactive astrocytes and microglia, and neuronal loss are all consistent pathological features of Alzheimer's disease (AD), a mechanistic link between these factors is yet to be clarified. Although the majority of past research has focused on fibrillar Aβ, soluble oligomeric Aβ species are now considered to be of major pathological importance in AD. Upregulation of GSH may be protective against the oxidative and neurotoxic effects of oligomeric Aβ. Depletion of the closed form of GSH in the hippocampus may be a potential early diagnostic biomarker for AD.
Glutathione | Alzheimer's disease
The third aspect of plant memory is epigenetics, where the plant, in response to a stimulus, undergoes histone and chromatin modification leading to changes in gene expression. These changes lead to a subsequent change in what proteins are made by the plant and establish a way for the plant to respond or be affected by stimuli from past experiences. These experiences can be passed down heritiarily from parent plant to offspring, giving an even longer term memory of a stimulus such as a stressor or other environmental stimuli. It is important to note that these changes are different from genetic changes because they can be reversed in response to new stimuli or environmental conditions.
Plant memory | Epigenetic memory
Plant memory is the ability of a plant to store information from previously experienced stimuli. While memory is a word often used in an human-centric light, this basic definition can be extended to many other organisms that exhibit delayed responses to a stimulus, including plants. Many examples can be seen across nature like from plants timing their leaves to rise in synchrony with the sun rising, to producing new leaves in the spring after overwintering. Plant memory is different from human and animal memory in that it does not involve the storage of memory in a brain structure, but does function similarly by using experiences to benefit the organism's survival later in life.
Plant memory | Introduction
One study examined dementia severity in elderly schizophrenic patients diagnosed with Alzheimer's disease and dementia versus elderly schizophrenic patients without any neurodegenerative disorders. In most cases, if schizophrenia is diagnosed, Alzheimer's disease or some form of dementia in varying levels of severity is also diagnosed. It was found that increased hippocampal neurofibrillary tangles and higher neuritic plaque density (in the superior temporal gyrus, orbitofrontal gyrus, and the inferior parietal cortex) were associated with increased severity of dementia. Along with these biological factors, when the patient also had the apolipoprotein E (ApoE4) allele (a known genetic risk factor for Alzheimer's disease), the neuritic plaques increased although the hippocampal neurofibrillary tangles did not.
Memory disorder | Aging
These genes control what proteins are made at certain times, as well as electrical and chemical signals that are produced to control motor proteins and other proteins. The overall result of these processes are subsequent changes in how the plant functions.
Plant memory | Biological clocks
Rather, age-related memory loss is characterized by dysfunctioning neurons. These results from MRI and other studies suggest that the primary initial target of normal aging is the DG, whereas the EC is relatively preserved.
Deficiency of RbAp48 protein and memory loss | Mechanism
REST expression strongly correlates with increased longevity. REST levels are highest in the brains of people who lived up to be 90 - 100s and remained cognitively intact. Levels stayed high specifically in the brain regions vulnerable to Alzheimer's, suggesting that they might be protected from dementia. It is assumed that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity. REST is also responsible for ischaemia induced neuronal cell death, in mouse models of brain ischaemia. Ischaemia, which results from reduced blood profusion of tissues, decreasing nutrient and oxygen supply, induces REST transcription and nuclear accumulation, leading to the epigenetic repression of neuronal genes leading to cell death.
RE1-silencing transcription factor | Function
Alzheimer's disease (AD) has historically been characterized by two major hallmarks: neurofibrillary tangles and amyloid-beta plaques. Neurofibrillary tangles are insoluble aggregates of tau proteins, and amyloid-beta plaques are extracellular deposits of the amyloid-beta protein. Current thinking in AD pathology goes beyond these two typical hallmarks to suggest that a significant portion of neurodegeneration in Alzheimer's is due to neuroinflammation. Activated microglia are seen in abundance in post-mortem AD brains. Current thought is that inflammatory cytokine-activated microglia cannot phagocytose amyloid-beta, which may contribute to plaque accumulation as opposed to clearance. Additionally, the inflammatory cytokine IL-1β is upregulated in AD and is associated with decreases of synaptophysin and consequent synaptic loss.
Neuroinflammation | Alzheimer's disease
Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in the stress response. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the "CRH" gene. Its main function is the stimulation of the pituitary synthesis of ACTH, as part of the HPA Axis. Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide derived from a 196-amino acid preprohormone. CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress. Increased CRH production has been observed to be associated with Alzheimer's disease and major depression, and autosomal recessive hypothalamic corticotropin deficiency has multiple and potentially fatal metabolic consequences including hypoglycemia.
Corticotropin-releasing hormone | Introduction
Routine blood tests are usually performed to rule out treatable causes. These tests include vitamin B, folic acid, thyroid-stimulating hormone (TSH), C-reactive protein, full blood count, electrolytes, calcium, renal function, and liver enzymes. Abnormalities may suggest vitamin deficiency, infection, or other problems that commonly cause confusion or disorientation in the elderly.
Dementia | Laboratory tests
Other neurological disorders such as Alzheimer's disease and Parkinson's disease can also affect memory and cognition. Hyperthymesia, or hyperthymesic syndrome, is a disorder that affects an individual's autobiographical memory, essentially meaning that they cannot forget small details that otherwise would not be stored. Korsakoff's syndrome, also known as Korsakoff's psychosis, amnesic-confabulatory syndrome, is an organic brain disease that adversely affects memory by widespread loss or shrinkage of neurons within the prefrontal cortex. While not a disorder, a common "temporary" failure of word retrieval from memory is the tip-of-the-tongue phenomenon. Sufferers of Anomic aphasia (also called Nominal aphasia or Anomia), however, do experience the tip-of-the-tongue phenomenon on an ongoing basis due to damage to the frontal and parietal lobes of the brain.
Memory | Disorders
Each of these types of human memory can be broken down to a basic process of retention and response. This pattern of processes can also be observed in plants. The most basic learning and memory functions in animals have been recorded in plants, and it is proposed that the development of these basic memory mechanisms were developed by an early organismal ancestor. Plants not only have developed conserved ways to use functioning memory, but some species have also developed unique ways to use memory function depending on their environment and life history. In this way, one can see that there is another similarity between the evolution of plant memory and the evolution of animal memory among the different species of each.The use of the term plant memory sparks some controversy in the field of plant biology, as some researchers believe this function only applies to organisms with a functioning brain.
Plant memory | Introduction
Of all the alkaloids, only galantamine has made it to therapeutic use in man, as the drug galantamine for Alzheimer's disease. Galantamine is an acetylcholine esterase inhibitor which crosses the blood brain barrier and is active within the central nervous system. Daffodils are grown commercially near Brecon in Powys, Wales, to produce galantamine.
Narcissus (plant) | Therapeutics
The bulbs of "Nerine bowdenii" contain ungeremine, a betaine-type alkaloid, and a number of other alkaloids. Ungeremine is an inhibitor of acetylcholinesterase, and as such may be of interest in research into treatment of Alzheimer's disease. Ungeremine also has been isolated from a number of related plant species, such as "Ungernia minor", "Ungernia spiralis", "Zephyranthes flava", "Crinum asiaticum", "Crinum augustum", "Pancratium maritimum" and "Hippeastrum solandriflorum".
Nerine bowdenii | Biochemistry
Melatonin is a natural hormone produced by the body to encode nighttime. Endogenous melatonin is secreted daily in all mammals beginning after sunset and ending just before sunrise. Melatonin’s chronobiotic property was initially suspected in the late 1980s when a high density of high-affinity melatonin receptors was discovered in the SCN. Little is known about the long-term effects of taking melatonin.
Chronobiotic | Melatonin
A review of evidence in 2005 suggested that PrP may have a normal function in maintenance of long-term memory. As well, a 2004 study found that mice lacking genes for normal cellular PrP protein show altered hippocampal long-term potentiation. A recent study that might explain why this is found that neuronal protein CPEB has a similar genetic sequence to yeast prion proteins. The prion-like formation of CPEB is essential for maintaining long-term synaptic changes associated with long term memory formation.
Prion | PrP and long-term memory
Some researchers believe that comparing plant functions that resemble memory in humans and other higher division organisms may be too direct of a comparison, while others believe that since the function of the two are essentially the same this comparison can act as a basis of knowledge for further understanding how these functions in plants work. In order to better define the parallels and differences of these functions in both plants and animals, more studies are necessary.
Plant memory | Introduction
The result of this abnormal processing is the accumulation of fragments of this protein, called amyloid β (Aβ). Aβ exists in both soluble and fibrillar forms. Misprocessing of APP results in the accumulation of soluble Aβ that, according to Rowan's hypothesis, impairs hippocampal LTP and may lead to the cognitive decline seen early in AD. AD may also impair LTP through mechanisms distinct from Aβ. For example, one study demonstrated that the enzyme PKMζ accumulates in neurofibrillary tangles, which are a pathologic marker of AD. PKMζ is an enzyme with critical importance in the maintenance of late LTP.
Long-term potentiation | Alzheimer's disease
Cortisol works with adrenaline (epinephrine) to create memories of short-term emotional events; this is the proposed mechanism for storage of flash bulb memories, and may originate as a means to remember what to avoid in the future. However, long-term exposure to cortisol damages cells in the hippocampus; this damage results in impaired learning.
Cortisol | Memory
Plaques are clumps of a protein called beta-amyloid. They may damage and destroy brain cells by interfering with cell-to-cell communication, among others. The collection of beta-amyloid on the outside of brain cells is thought to be implicated in the cause of this disease. Tangles are threads of another protein, tau. Tau twist into abnormal tangles inside brain cells, resulting in failure of the transport system, which is also implicated in the death of brain cells. The brain relies on this internal support and transport system in order to carry nutrients and essential materials, requiring the normal structure and functioning of tau.
Visual selective attention in dementia | Alzheimer's disease
Alzheimer's has been shown to have a hormonal component, which could possibly be used as a method to prevent the disease. Male contraceptives utilizing sex hormones approach the problem in a similar way. The HPG axis can also be suppressed by GnRH antagonists or continuous administration of GnRH agonist, such as in the following applications
Hypothalamic–pituitary–gonadal axis | Suppression
The secretion of many hormones is affected by sleep-wake cycles. For example, melatonin, a hormonal timekeeper, is considered a strongly circadian hormone, whose secretion increases at dim light and peaks during nocturnal sleep, diminishing with bright light to the eyes. In some organisms melatonin secretion depends on sleep, but in humans it is independent of sleep and depends only on light level. Of course, in humans as well as other animals, such a hormone may facilitate coordination of sleep onset. Similarly, cortisol and thyroid stimulating hormone (TSH) are strongly circadian and diurnal hormones, mostly independent of sleep. In contrast, other hormones like growth hormone (GH) & prolactin are critically sleep-dependent, and are suppressed in the absence of sleep.
Neuroscience of sleep | Endocrine function
Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with anterograde amnesia cannot remember things for long periods of time. These two types are not mutually exclusive; both can occur simultaneously. Case studies also show that amnesia is typically associated with damage to the medial temporal lobe. In addition, specific areas of the hippocampus (the CA1 region) are involved with memory. Research has also shown that when areas of the diencephalon are damaged, amnesia can occur. Recent studies have shown a correlation between deficiency of RbAp48 protein and memory loss. Scientists were able to find that mice with damaged memory have a lower level of RbAp48 protein compared to normal, healthy mice.
Amnesia | Introduction
Notably high melatonin concentrations have been measured in popular beverages such as coffee, tea, wine, and beer, and crops including corn, rice, wheat, barley, and oats. In some common foods and beverages, including coffee and walnuts, the concentration of melatonin has been estimated or measured to be sufficiently high to raise the blood level of melatonin above daytime baseline values. Although a role for melatonin as a plant hormone has not been clearly established, its involvement in processes such as growth and photosynthesis is well established. Only limited evidence of endogenous circadian rhythms in melatonin levels has been demonstrated in some plant species and no membrane-bound receptors analogous to those known in animals have been described.
Melatonin | Plants
This gene encodes the MT protein, one of two high-affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This receptor is a G protein-coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive effects of melatonin.
Melatonin receptor 1A | Function
"Alternatively, episodes of TEA might themselves give rise to structural damage within the hippocampus or related structures, which could disrupt long term consolidation." One study found "subtle hippocampal volume loss" in patients with TEA, but the atrophy did not correspond to measures of either ALF or autobiographical memory loss, suggesting "a more diffuse physiological basis rather than being a consequence of structural damage." Antiepileptic drugs sometimes affect memory. However, this is unlikely to be the cause of ALF in TEA, as patients tend to report memory problems before they start taking the antiepileptic drugs and can experience improvement in their memory after taking them.
Transient epileptic amnesia | Accelerated long-term forgetting (ALF)
Age-related memory loss, sometimes described as "normal aging" (also spelled "ageing" in British English), is qualitatively different from memory loss associated with types of dementia such as Alzheimer's disease, and is believed to have a different brain mechanism.
Memory and aging | Introduction
The hippocampus is a portion of the limbic system responsible for memory and spatial navigation. Additionally, certain VDR haplotypes were detected with increased frequency in patients with Alzheimer's disease while other VDR haplotypes were detected with decreased frequency, suggesting that specific haplotypes may increase or decrease risk of developing Alzheimer's. It is hypothesized that this lack of VDRs in the hippocampus prevents the proper functioning (ie. memory) of this structure.
Vitamin D and neurology | Dementia: Alzheimer's disease
Psychological symptoms include anxiety, poor memory, inability to concentrate, depressive mood, irritability, mood swings, and less interest in sexual activity. Menopause-related cognitive impairment can be confused with the mild cognitive impairment that precedes dementia. Tentative evidence has found that forgetfulness affects about half of menopausal women, and is probably caused by the effects of declining estrogen levels on the brain, or perhaps by reduced blood flow to the brain during hot flashes.
Menopause | Mood and memory effects
Alzheimer's disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in the cerebral cortex and certain subcortical structures, resulting in gross atrophy of the temporal lobe, parietal lobe, and parts of the frontal cortex and cingulate gyrus. AD pathology is primarily characterized by the presence of senile plaques and neurofibrillary tangles. Plaques are made up of small peptides, typically 39–43 amino acids in length, called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane.
Neurodegeneration | Alzheimer's disease
Alzheimer’s Disease (AD) is a neurodegenerative condition characterized by two hallmarks: senile plaques and the neurofibrillary tangle. Senile plaques are extracellular aggregations of amyloid-b (Aβ) protein. Neurofibrillary tangles are collections of hyperphosphorylated tau protein associated with microtubules found within neurons. Senile plaques and neurofibrillary tangles are widespread throughout brain tissue and mirror other pathological changes associated with AD.
Cell-Cycle Hypothesis of Alzheimer's Disease | Introduction
Knockdown of ethylene biosynthesis genes was consistent with increased corolla longevity; inversely, up-regulation of ethylene biosynthesis gene transcription factors were consistent with a more rapid senescence of the corolla.
Ethylene as a plant hormone | Corolla senescence
There is a growing amount of information that has shown that memory depends largely on the brain's synaptic plasticity, with a large part of this being dependent on its ability to maintain long-term potentiation (LTP). Studies on LTP have also started to indicate that there are several molecular mechanisms that may be at the basis of memory storage. Recovering methamphetamine (METH) addicts have reported that the sight of certain objects such as a lighter, gum or drug paraphernalia can cause massive cravings that can sometimes lead to a break in their mental strength and cause them to relapse. This indicates that long-term memories can be called upon by various different associations that were made with the memory without the conscious effort of the person.
Memory erasure | Disruption of molecular mechanisms
In animals, biosynthesis of melatonin occurs through hydroxylation, decarboxylation, acetylation and a methylation starting with -tryptophan. -tryptophan is produced in the shikimate pathway from chorismate or is acquired from protein catabolism. First -tryptophan is hydroxylated on the indole ring by tryptophan hydroxylase to produce 5-hydroxytryptophan. This intermediate (5-HTP) is decarboxylated by pyridoxal phosphate and 5-hydroxytryptophan decarboxylase to produce serotonin. Serotonin is itself an important neurotransmitter, but is also converted into "N"-acetylserotonin by serotonin "N"-acetyltransferase with acetyl-CoA. Hydroxyindole "O"-methyltransferase and "S"-adenosyl methionine convert "N"-acetylserotonin into melatonin through methylation of the hydroxyl group. In bacteria, protists, fungi, and plants, melatonin is synthesized indirectly with tryptophan as an intermediate product of the shikimate pathway.
Melatonin | Biosynthesis
Mansuy initially worked on the molecular mechanisms of memory using mouse models. Her team revealed the specific molecules that allow the adult brain to forget through constraining memory formation and storage. It identified protein phosphatase 1 (PP1) and calcineurin as such molecular suppressors and demonstrated that these molecules need to be inhibited through training to relieve their suppressing action on neuronal activity necessary for memorisation. Her team was also able to demonstrate the detrimental effects of the excess of these molecules in the diseased and aged brain, highlighting their link to memory deficits and cognitive decline in aging. Another important finding was that PP1 is a key epigenetic regulator in neurons that controls the post-translational modification of histones and therefore genome activity.
Isabelle Mansuy | Research
The temporary expulsion of magnesium frees NMDA receptors to release calcium in the cell, a signal that leads to gene transcription and the construction of reinforcing proteins. For more information, see long-term potentiation (LTP). One of the newly synthesized proteins in LTP is also critical for maintaining long-term memory. This protein is an autonomously active form of the enzyme protein kinase C (PKC), known as PKMζ. PKMζ maintains the activity-dependent enhancement of synaptic strength and inhibiting PKMζ erases established long-term memories, without affecting short-term memory or, once the inhibitor is eliminated, the ability to encode and store new long-term memories is restored.
Memory | Genetic underpinnings
Alzheimer's Disease is characterized by progressive memory impairment and decline, usually beginning short-term memory. As it is a progressive disease, Alzheimer's usually begins with memory errors before proceeding to long-term memory stores. One form of memory error occurs in contrast to the theory of retrieval cues in being a reason for the occurrence of memory errors. As noted above, memory errors may be due to the lack of cues that can trigger a memory trace and bring it to awareness. However, studies have shown that the opposite may be true for patients with Alzheimer's, such that cues may actually decrease perform on priming tasks.
Memory error | Alzheimer's Disease
Patients also demonstrate errors known as misattribution errors, otherwise known as source confusion. However, studies show that these misattribution errors are dependent on whether the task is a familiarity or recollection task. Although patients tend to exhibit a higher level of false recognitions than control groups, researchers have shown that they may exhibit less false-recognition early in the test due to familiarity being slower to develop. However, the observation of increasing instances of misattribution errors can be seen once familiarity does occur. This may be related to the retrieval cue speculation, in that familiar memories often contain cues we know, and thus may be the reason why familiarity can contribute to memory errors.
Memory error | Alzheimer's Disease