Rossetti Clara, Cherix Antoine, Guiraud Laetitia F, Cardinaux Jean-René
Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland.
Service of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Front Mol Neurosci. 2022 Feb 15;15:810641. doi: 10.3389/fnmol.2022.810641. eCollection 2022.
Depression and obesity are major public health concerns, and there is mounting evidence that they share etiopathophysiological mechanisms. The neurobiological pathways involved in both mood and energy balance regulation are complex, multifactorial and still incompletely understood. As a coactivator of the pleiotropic transcription factor cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 1 (CRTC1) has recently emerged as a novel regulator of neuronal plasticity and brain functions, while CRTC1 dysfunction has been associated with neurodegenerative and psychiatric diseases. This review focuses on recent evidence emphasizing the critical role of CRTC1 in the neurobiology of depression and comorbid obesity. We discuss the role of CRTC1 downregulation in mediating chronic stress-induced depressive-like behaviors, and antidepressant response in the light of the previously characterized knockout mouse model of depression. The putative role of CRTC1 in the alteration of brain energy homeostasis observed in depression is also discussed. Finally, we highlight rodent and human studies supporting the critical involvement of CRTC1 in depression-associated obesity.
抑郁症和肥胖症是主要的公共卫生问题，而且越来越多的证据表明它们具有共同的病因病理生理机制。情绪和能量平衡调节所涉及的神经生物学途径复杂、多因素且仍未完全被理解。作为多效转录因子环磷酸腺苷反应元件结合蛋白（CREB）的共激活因子，CREB调节的转录共激活因子1（CRTC1）最近已成为神经元可塑性和脑功能的新型调节因子，而CRTC1功能障碍与神经退行性疾病和精神疾病有关。本综述重点关注近期证据，这些证据强调了CRTC1在抑郁症和合并肥胖症神经生物学中的关键作用。我们根据先前表征的抑郁症基因敲除小鼠模型，讨论CRTC1下调在介导慢性应激诱导的抑郁样行为和抗抑郁反应中的作用。还讨论了CRTC1在抑郁症中观察到的脑能量稳态改变中的假定作用。最后，我们重点介绍支持CRTC1在抑郁症相关肥胖症中起关键作用的啮齿动物和人类研究。
