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Salk researchers have discovered that genes that are switched on early in brain development to sever connections between neurons as the brain fine-tunes, are again activated in aging neuronal support cells called astrocytes. Astrocytes may be good therapeutic targets to prevent or reverse the effects of normal aging.
Neuroscientists know that in the young, developing brain, synapses are being activated and deactivated, while in the adult brain they are mostly stable. But in aging brains, neurons start to lose connections and don’t communicate as well. Allen and graduate student Matthew Boisvert wondered whether the changes to synapses and neuronal communication during aging might be related to changes in astrocytes.
To find out, the duo decided to compare gene expression in astrocytes in the adult brain versus the aged brain in mice. This would give them an idea of which genes are active at the two stages.o Researchers compare four-month-old mice, who in mouse years are adults, to two-year-old mice, who are quite elderly. They used a molecular technology called ribo-tag that allowed him to find out which genes were being made into proteins by astrocytes. It works by isolating the protein-making machines of cells (called ribosomes), which turn mRNA copies of DNA (genes) into proteins.
By taking a sort of molecular snapshot of an astrocyte’s ribosomes, it’s possible to see all the mRNA copies in progress and thus know which genes are active. To develop a comprehensive view of astrocyte gene expression, the duo used the technique in four very different areas of the mouse brain: two regions of the cortex and the hypothalamus and cerebellum.
To their surprise, they found that most of the properties that make an astrocyte an astrocyte didn’t change much with age-gene expression was fairly consistent with time. But what did change: genes that during development would normally cause the loss of connections between neurons were switched on again in the aging astrocytes.
This suggests that there’s some sort of genetic program that’s being reactivated in these astrocytes as they age that’s causing neurons to lose their connections with each other. Interestingly, the areas in which astrocytes looked the most different were brain areas where neurons are known to function notably less well with age or even to die-the cerebellum and the hypothalamus. This may explain why metabolism decreases and coordination gets worse with age, because these are functions that are coordinated by the hypothalamus and cerebellum.
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