Epigenetic Mechanisms of Depression

描述（由申请人提供）：这个新的Conte中心的目标是最大限度地利用染色质生物学的最新进展，即所谓的表观遗传学，从根本上增加我们对大脑中导致抑郁症和介导抗抑郁反应的长期异常的理解。我们的工作将集中在关键的大脑边缘区域，伏隔核（NAc）和前额皮质（PFC）的几个区域，这些区域在健康和疾病的情绪控制中有直接的影响。该中心由四所不同大学的四个项目组成。四个pi， Eric Nestler（西奈山），

DESCRIPTION (provided by applicant): The objective of this new Conte Center is to take maximal advantage of recent advances in chromatin biology, so-called epigenetics, to fundamentally increase our understanding of the long-lasting abnormalities in the brain that cause depression and that mediate antidepressant responses. Our work will focus on key limbic brain regions, nucleus accumbens (NAc) and several areas of prefrontal cortex (PFC), which have been implicated directly in the control of mood in health and disease. The Center is composed of four Projects at four different universities. The four PIs, Eric Nestler (Mount Sinai), Schahram Akbarian (UMass), David Allis (Rockefeller), and Carol Tamminga (UT Southwestern), are leaders in their fields who have an established history of effective collaboration and will use their complementary expertise and approaches to chart a multidisciplinary course in the proposed research. Projects 1, 2, and 3, lead by Drs. Nestler, Akbarian, and Allis, respectively, will characterize the role of epigenetic mechanisms within the brain's limbic regions in a range of animal models of depression over the life cycle of the animals. Project 4, lead by Dr. Tamminga, will translate these findings in animals to human postmortem brain tissue and thereby provide essential validation of the basic research for human depression. The Center is supported by three Cores, an Administrative Core to oversee and coordinate the Center's operations; a Chromatin and Gene Analysis Core to provide advanced state-of-the-art methods and bioinformatics to characterize genome-wide regulation of chromatin modifications in limbic regions in depression and antidepressant action; and an Animal Models Core to provide the most sophisticated animal models of depression along with the advanced tools (viral-mediated gene transfer and inducible mutations in mice) to manipulate individual genes of interest within limbic structures and thereby provide causal evidence for the involvement of epigenetic regulation in depression-related phenomena. We are very excited about this novel and pioneering investigation of the epigenetic underpinnings of depression, which we believe will help drive the field toward dramatically better treatments and diagnostic tests for depression and other stress-related illnesses.