Metabolic Enzyme Fuels Molecular Machinery of Memory

저자：   업로드：2017-06-05  조회수：

    Understanding how memories are made, retrieved, and eventually fade over a lifetime is the stuff of poems and song. To medical researchers, solving the mysteries of memory is even more elusive. Researchers surmise that "laying down" a new memory and storing an old memory both involve making proteins at the space, or synapse, where one neuron meets another. But forming these also requires new gene expression in the cell nucleus, where DNA is stored and genes are "read" to establish cell-specific functions.

    Researchers from the Perelman School of Medicine at the University of Pennsylvania have discovered, in the mouse brain that a key metabolic enzyme works directly within the nucleus of neurons to turn genes on or off when new memories are being established.

    In short, the researchers have shown that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) directly regulates histone acetylation in neurons and spatial memory in mammals. This finding, the researchers suggest, reveals that cellular metabolism, gene regulation, and neural plasticity are all connected.

    Additional details appeared May 31 in Nature, in an article entitled “Acetyl-CoA Synthetase Regulates Histone Acetylation and Hippocampal Memory.” These details include descriptions of the regulation of histone acetylation and transcriptional dynamics during differentiation in vitro and in response to behavioral training in vivo. Ultimately, the article makes a case that a link exists between acetyl-CoA generation “on site” at chromatin for histone acetylation and the transcription of key neuronal genes.

    “In a neuronal cell culture model, ACSS2 increases in the nuclei of differentiating neurons and localizes to upregulated neuronal genes near sites of elevated histone acetylation,” the article’s authors wrote. “A decrease in ACSS2 lowers nuclear acetyl-CoA levels, histone acetylation, and responsive expression of the cohort of neuronal genes."

    “In adult mice, attenuation of hippocampal ACSS2 expression impairs long-term spatial memory, a cognitive process that relies on histone acetylation. A decrease in ACSS2 in the hippocampus also leads to defective upregulation of memory-related neuronal genes that are pre-bound by ACSS2.”

    This work was accomplished by a team of scientists led by Shelley L. Berger, Ph.D., the Daniel S. Och University Professor in the departments cell and developmental biology and biology and director of the Penn Epigenetics Program. She summarized the team’s findings as follows: "ACSS2 'fuels' a whole machinery of gene e

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