What a mother mouse eats during pregnancy and lactation can change fatty-acid metabolism in her pups. Also this week: nanoparticles may enable deep-tissue photodynamic therapy.
Baby's Epigenetics Affected by Maternal Diet
Not only are you what you eat, so is your offspring, suggested a mouse-model study in the Journal of the Federation of American Societies for Experimental Biology.
What female mice ate during gestation and lactation substantially altered their offspring's metabolism of essential fatty acids, including omega-3 and omega-6. The effect appeared to be mediated by changes in gene regulation detected in the pups' livers.
Diabetes, obesity, cancer, and immune disorders could be affected by this mechanism, the University of North Carolina researchers suggested.
"New York City may be laughed at by some for banning large, sugary sodas and for encouraging a healthy diet," Gerald Weissmann, MD, editor-in-chief of the journal, wrote in a press release. "As we begin to understand the effects of diet on epigenetics, New York may go from being considered a funny 'nanny-state' to becoming appreciated as a public health visionary."
Light-Therapy Puzzle Has Nanosolution
Deep-seated tumors proved susceptible to penetrating ultraviolet (UV) light delivered by silica-coated, fluorescent nanoparticles, studies involving mouse models showed.
Laser-activated upconversion nanoparticles (UCNs) significantly inhibited the growth of implanted melanoma cells. In contrast, the cancer cells developed into tumors within 2 to 3 weeks in animals that received UCNs without exposure to a laser beam.
The UCNs, coupled to two photosensitizers, serve as nanotransducers to convert deep-penetrating near-infrared light to cytotoxic UV radiation. The UV light induces tumor-cell death by altering the tumor's gene expression, as reported online in Nature Medicine.
The nanoparticle technology overcomes a principal limitation of photodynamic therapy: its inability to penetrate very far below the skin surface.
"As the first demonstration, to the best of our knowledge, of the photosensitizer-loaded UCN as an in vivo-targeted photodynamic therapy agent, this finding may serve as a platform for future noninvasive deep-cancer therapy," Yong Zhang, PhD, of the National University of Singapore, and co-authors wrote in conclusion.
-- Charles Bankhead
Closing the Gate on Seizures
Dysfunction of a cellular gate in the brain allows the overload of excitatory signals that result in seizures, researchers demonstrated in a mouse model of epilepsy.
That the development of epilepsy is characterized by the accretion of abnormal granule cells in the dentate gyrus of the hippocampus has long been recognized. Now, however, researchers from Cincinnati Children's Hospital have shown that a gene deletion in PTEN leads to morphologic changes in granule cells in mice, which, in turn, results in overactivation of the mTOR pathway.
Even when less than 10% of the dentate gyrus granule cells developed abnormalities such as excess dendritic spines and basal dendrites, the mice became progressively epileptic – for the first time revealing a precise, plausible mechanism for epileptogenesis, the researchers reported in Neuron.
To confirm the involvement of granule cells and the mTOR pathway in disrupting the hippocampal excitatory gate, Steven Danzer and colleagues treated the affected mice with rapamycin, which blocks that signaling pathway, and the seizures stopped.
Because the aberrant granule cells have also been identified in humans with temporal lobe epilepsy, this mTOR pathway may represent a new, specific target for the prevention of seizures in humans, the researchers suggested.
-- Nancy Walsh
Turn Left at the Hippocampus
Human brains appear to have a strong underlying common blueprint, coupled with a high degree of biochemical complexity, according to investigators developing the first detailed genetic map of the brain. Researchers led by Michael Hawrylycz, PhD, of the Allen Institute for Brain Science in Seattle, analyzed genetic transcription patterns and molecular structures of two human brains and half of a third.
In the Sept. 20 issue of Nature, they reported on the development of the map and some important first findings, including the fact that 84% of all genes are turned on somewhere in the brain but that expression patterns don't vary much from one brain to another. As well, the investigators found, the right and left hemispheres don't differ much in their molecular structures, suggesting that any functional variations arise from other differences in size or circuitry.
Another important finding is that some gene expression patterns that are consistent in humans vary markedly from those found in animals often used as models for human disease. In the human hippocampus, for instance, the protein binding gene CALB1 is expressed mainly in a single region, but in both mice and rhesus monkeys it is expressed throughout the structure.
The data set is available online for study, Hawrylycz and colleagues reported, and they are now trying to analyze more brains of varying sexes and ethnicities in order to deepen the analysis.
Heparin Impairs Stem Cell Therapy
Intracoronary delivery of bone marrow-derived mononuclear cells (BMCs) following a heart attack carries a clotting risk, but giving an anticoagulant may undermine the therapy.
In mouse experiments, heparin adversely affected the homing activity of BMCs, whereas the direct thrombin inhibitor bivalirudin (Angiomax) did not, according to Florian H. Seeger, MD, of Goethe University in Frankfurt, Germany, and colleagues.
Heparin did this by binding to stromal cell–derived factor 1 and its receptor, chemokine receptor 4, thereby reducing the number of BMCs that can find their way to infarcted areas and induce neovascularization.
In addition, heparin is often added to BMCs during processing and storage to prevent clumping. But in vivo experiments showed that heparin disrupted the functional capacity of BMCs, including the ability to form colonies.
These findings "might be important for the interpretation of existing clinical trial data and the design of future studies," Seeger and colleagues wrote in Circulation Research.