Ependymal cells-CSF flow regulates stress-induced depression.
Ependymal cells-CSF flow regulates stress-induced depression.
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DOI：
10.1038/s41380-021-01202-1
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发表时间：
2021-12
影响因子：
11
通讯作者：
Greengard P
中科院分区：
文献类型：
--
作者：
Seo JS;Mantas I;Svenningsson P;Greengard P
重度抑郁障碍(MDD)是一种严重的、常见的情绪障碍。虽然脑脊液(CSF)流量减少会对老龄化人口和发育过程中的大脑新陈代谢和液体平衡造成不利影响，但只有间接证据将脑脊液循环异常与许多疾病联系起来，包括神经、神经退行性疾病和精神障碍，如焦虑和抑郁。在这里，我们显示了非常高浓度的p11作为抑郁症的关键分子决定因素，室管膜细胞中的p11在MDD患者和两种慢性应激诱导的抑郁症小鼠模型中显著减少，如束缚和社交隔离。室管膜细胞中p11基因的缺失会导致室管膜平面细胞极化(PCP)方向紊乱、脑脊液流量减少以及抑郁和焦虑样行为。P11在本质上控制着PCP核心基因，而PCP核心基因调节脑脊液流动。P11在室管膜细胞中的病毒表达特异性地挽救了由于p11缺失而导致的病理生理和行为缺陷。综上所述，我们的结果确定了室管膜细胞驱动的脑脊液流动在情绪障碍中的新作用和关键分子决定因素，并为应激相关神经、神经退行性疾病和精神疾病的治疗提供了一种新的策略。
Major depressive disorder (MDD) is a severe, common mood disorder. While reduced cerebrospinal fluid (CSF) flow adversely affects brain metabolism and fluid balance in the aging population and during development, only indirect evidence links aberrant CSF circulation with many diseases including neurological, neurodegenerative, and psychiatric disorders, such as anxiety and depression. Here we show a very high concentration of p11 as a key molecular determinant for depression in ependymal cells, which is significantly decreased in patients with MDD, and in two mouse models of depression induced by chronic stress, such as restraint and social isolation. The loss of p11 in ependymal cells causes disoriented ependymal planar cell polarity (PCP), reduced CSF flow, and depression-like and anxiety-like behaviors. p11 intrinsically controls PCP core genes, which mediates CSF flow. Viral expression of p11 in ependymal cells specifically rescues the pathophysiological and behavioral deficits caused by loss of p11. Taken together, our results identify a new role and a key molecular determinant for ependymal cell-driven CSF flow in mood disorders and suggest a novel strategy for development of treatments for stress-associated neurological, neurodegenerative, and psychiatric disorders.
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影响因子：
15.9
作者：
Ohata S;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A
DOI：
10.1126/science.abb8739
发表时间：
2020-10-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nedergaard M;Goldman SA
通讯作者：
Goldman SA
影响因子：
17.1
作者：
Iliff JJ;Wang M;Liao Y;Plogg BA;Peng W;Gundersen GA;Benveniste H;Vates GE;Deane R;Goldman SA;Nagelhus EA;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
21.3
作者：
Guirao, Boris;Meunier, Alice;Spassky, Nathalie
通讯作者：
Spassky, Nathalie
影响因子：
64.8
作者：
Gong, SC;Zheng, C;Heintz, N
通讯作者：
Heintz, N