東京大学定量生命科学研究所分子神経生物学研究分野Institute for Quantitative Biosciences, The University of Tokyo― 219 ―We are exposed to a variety of stresses in our lives, including aging, diseases, and social interactions. Each stress alters brain function over the long term afterward, but the mechanisms are not always clear. The epigenome is multi-scale information, from nanometre-level structures such as DNA and chemical modifications on histones to micrometer-level structures such as the three-dimensional structure of chromatin and nuclear structure; these chemical modifications and structures alter gene function through the regulation of gene transcription states and thereby altering cellular function. I, therefore, hypothesized that the stress experience might alter the epigenome of neurons, cells that play an important role in the brain and that this finally changes brain function by altering the state of gene expression. In this study, I aimed to understand stress-induced changes in brain function by testing this hypothesis.Among various stresses, aging increases the risk of disease in many tissues and, in the brain, increases the frequency of various neurological disorders such as neurodegenerative diseases and dementia. Among the age-related intracellular changes, abnormalities in nuclear morphology are commonly observed in many cells, but changes in the nuclear morphology of age-related neurons were unknown. Therefore, as a first step to investigate the neuronal epigenomic changes induced by the stress of aging, we observed the nuclear morphology of neurons in the visual cortex of aged mice, which had a more infolded nuclear shape than that of young mice. In addition, time-lapse imaging of the nuclei of visual cortex neurons in response to visual stimulation showed that the nuclei of young mice were infolded within 10-15 min, whereas those of aged mice were not. The nuclei of neurons in aged mice were measured by atomic force microscopy and found to be stiffer than those in young mice.These results indicate that ageing reduces neuronal nuclear dynamics (morphological flexibility and softness). The changes in the nucleus, the largest structure in the epigenomic information, support my hypothesis Abstractニューロンのエピゲノムからストレス反応を理解・制御するThe role of epigenome of neurons in stress responses岸 雄介Yusuke Kishi
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