Coda Davide Martino, Gräff Johannes
Laboratory of Neuroepigenetics, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Front Mol Neurosci. 2020 Dec 3;13:205. doi: 10.3389/fnmol.2020.589109. eCollection 2020.
Over the last two decades, the explosion of experimental, computational, and high-throughput technologies has led to critical insights into how the brain functions in health and disease. It has become increasingly clear that the vast majority of brain activities result from the complex entanglement of genetic factors, epigenetic changes, and environmental stimuli, which, when altered, can lead to neurodegenerative and neuropsychiatric disorders. Nevertheless, a complete understanding of the molecular mechanisms underlying neuronal activities and higher-order cognitive processes continues to elude neuroscientists. Here, we provide a concise overview of how the interaction between the environment and genetic as well as epigenetic mechanisms shapes complex neuronal processes such as learning, memory, and synaptic plasticity. We then consider how this interaction contributes to the development of neurodegenerative and psychiatric disorders, and how it can be modeled to predict phenotypic variability and disease risk. Finally, we outline new frontiers in neurogenetic and neuroepigenetic research and highlight the challenges these fields will face in their quest to decipher the molecular mechanisms governing brain functioning.
在过去二十年中，实验技术、计算技术和高通量技术的迅猛发展，使我们对大脑在健康和疾病状态下的功能有了至关重要的认识。越来越明显的是，绝大多数大脑活动源于遗传因素、表观遗传变化和环境刺激的复杂交织，这些因素一旦改变，就可能导致神经退行性疾病和神经精神疾病。然而，神经科学家们仍未完全理解神经元活动和高阶认知过程背后的分子机制。在此，我们简要概述环境与遗传以及表观遗传机制之间的相互作用如何塑造学习、记忆和突触可塑性等复杂的神经元过程。然后，我们探讨这种相互作用如何导致神经退行性疾病和精神疾病的发生，以及如何通过建模来预测表型变异性和疾病风险。最后，我们概述神经遗传学和神经表观遗传学研究的新前沿，并强调这些领域在试图破译控制大脑功能的分子机制时将面临的挑战。
