Dendritic remodeling of D1 neurons by RhoA/Rho-kinase mediates depression-like behavior.
Dendritic remodeling of D1 neurons by RhoA/Rho-kinase mediates depression-like behavior.
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DOI：
10.1038/s41380-018-0211-5
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发表时间：
2020-05
影响因子：
11
通讯作者：
Lobo MK
中科院分区：
文献类型：
--
作者：
Fox ME;Chandra R;Menken MS;Larkin EJ;Nam H;Engeln M;Francis TC;Lobo MK
抑郁症会改变大脑奖励回路的结构和功能。临床前证据表明，伏隔核 (NAc) 中的中型多棘神经元 (MSN) 具有结构可塑性，但其分子机制和行为意义尚不清楚。在这里，我们报告说，在遭受社交失败压力的小鼠中，含有 MSN 的 D1 受体的萎缩与社交回避密切相关，而 D2 受体的萎缩则不然。 D1-MSN 萎缩是由 GTPase RhoA 及其效应 Rho 激酶的细胞类型特异性上调引起的。活性 RhoA 的药理学和遗传减少可通过防止 D1-MSN 树突状乔木的损失来预防应激导致的抑郁结果。激活 RhoA 的药理学和遗传促进作用可通过减少 D1-MSN 树突乔木来增强抑郁结果，并且足以在没有压力的情况下促进抑郁样行为。在慢性社交失败压力后，使用 Rho 激酶抑制剂 Y-27632 进行长期治疗可通过恢复 D1-MSN 树突复杂性来逆转抑郁样行为。总而言之，我们的数据表明 RhoA 和 Rho 激酶通过 NAc D1-MSN 的树突重塑来介导抑郁样行为，并可能成为新抑郁症治疗的有用靶标。
Depression alters the structure and function of brain reward circuitry. Preclinical evidence suggests that medium spiny neurons (MSNs) in the nucleus accumbens (NAc) undergo structural plasticity, however the molecular mechanism and behavioral significance is poorly understood. Here we report that atrophy of D1, but not D2 receptor containing MSNs is strongly associated with social avoidance in mice subject to social defeat stress. D1-MSN atrophy is caused by cell-type specific upregulation of the GTPase RhoA and its effector Rho-kinase. Pharmacologic and genetic reduction of activated RhoA prevents depressive outcomes to stress by preventing loss of D1-MSN dendritic arbor. Pharmacologic and genetic promotion of activated RhoA enhances depressive outcomes by reducing D1-MSN dendritic arbor and is sufficient to promote depressive-like behaviors in the absence of stress. Chronic treatment with Rho-kinase inhibitor Y-27632 after chronic social defeat stress reverses depression-like behaviors by restoring D1-MSN dendritic complexity. Taken together, our data indicate functional roles for RhoA and Rho-kinase in mediating depression-like behaviors via dendritic remodeling of NAc D1-MSNs and may prove a useful target for new depression therapeutics.
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DOI：
10.1523/jneurosci.1758-09.2009
发表时间：
2009-09-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Covington HE 3rd;Maze I;LaPlant QC;Vialou VF;Ohnishi YN;Berton O;Fass DM;Renthal W;Rush AJ 3rd;Wu EY;Ghose S;Krishnan V;Russo SJ;Tamminga C;Haggarty SJ;Nestler EJ
通讯作者：
Nestler EJ
β-catenin通过DICER1/microRNA调节介导了应力弹性。
影响因子：
64.8
作者：
Dias, Caroline;Feng, Jian;Sun, Haosheng;Shao, Ning yi;Mazei-Robison, Michelle S.;Damez-Werno, Diane;Scobie, Kimberly;Bagot, Rosemary;LaBonte, Benoit;Ribeiro, Efrain;Liu, XiaoChuan;Kennedy, Pamela;Vialou, Vincent;Ferguson, Deveroux;Pena, Catherine;Calipari, Erin S.;Koo, Ja Wook;Mouzon, Ezekiell;Ghose, Subroto;Tamminga, Carol;Neve, Rachael;Shen, Li;Nestler, Eric J.
通讯作者：
Nestler, Eric J.
影响因子：
11
作者：
Francis TC;Chandra R;Gaynor A;Konkalmatt P;Metzbower SR;Evans B;Engeln M;Blanpied TA;Lobo MK
通讯作者：
Lobo MK
影响因子：
16.2
作者：
Chandra R;Engeln M;Schiefer C;Patton MH;Martin JA;Werner CT;Riggs LM;Francis TC;McGlincy M;Evans B;Nam H;Das S;Girven K;Konkalmatt P;Gancarz AM;Golden SA;Iñiguez SD;Russo SJ;Turecki G;Mathur BN;Creed M;Dietz DM;Lobo MK
通讯作者：
Lobo MK
影响因子：
4.8
作者：
Chandra R;Lenz JD;Gancarz AM;Chaudhury D;Schroeder GL;Han MH;Cheer JF;Dietz DM;Lobo MK
通讯作者：
Lobo MK