Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens.
Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens.
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DOI：
10.1038/tp.2013.39
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发表时间：
2013-06-04
影响因子：
6.8
通讯作者：
Sousa N
中科院分区：
文献类型：
--
作者：
Bessa JM;Morais M;Marques F;Pinto L;Palha JA;Almeida OF;Sousa N
越来越多的证据表明，伏核(NAC)在抑郁症的病理生理过程中起着重要作用。由于NAC是奖赏神经回路中的关键组成部分，因此有人推测，快感缺失是抑郁症的核心症状，可能与这一大脑区域的功能障碍有关。在慢性轻度应激反应中表现出无享乐行为的大鼠(在蔗糖消耗实验中测量)，观察了神经元的形态和可塑性相关分子在NAC的表达。为了证明我们的测量与抑郁的相关性，我们测试了观察到的变化是否对抗抑郁药(丙咪嗪和氟西汀)逆转敏感。数据显示，表现出享乐行为的动物表现出NAC中棘神经元的肥大，同时，脑源性神经营养因子、神经细胞黏附分子和突触蛋白突触蛋白1的基因表达增加。重要的是，抗抑郁药物逆转应激性快感丧失与NAC基因表达模式和树突形态的恢复有关。利用抑郁症的动物模型，我们证明了应激诱导的享乐行为与神经元形态和NAC基因表达谱的特定变化有关，而这些变化在抗抑郁药物治疗后有效地逆转。
There is accumulating evidence that the nucleus accumbens (NAc) has an important role in the pathophysiology of depression. As the NAc is a key component in the neural circuitry of reward, it has been hypothesized that anhedonia, a core symptom of depression, might be related to dysfunction of this brain region. Neuronal morphology and expression of plasticity-related molecules were examined in the NAc of rats displaying anhedonic behavior (measured in the sucrose-consumption test) in response to chronic mild stress. To demonstrate the relevance of our measurements to depression, we tested whether the observed changes were sensitive to reversal with antidepressants (imipramine and fluoxetine). Data show that animals displaying anhedonic behavior display an hypertrophy of medium spiny neurons in the NAc and, in parallel, have increased expression of the genes encoding for brain-derived neurotrophic factor, neural cell adhesion molecule and synaptic protein synapsin 1. Importantly, the reversal of stress-induced anhedonia by antidepressants is linked to a restoration of gene-expression patterns and dendritic morphology in the NAc. Using an animal model of depression, we show that stress induces anhedonic behavior that is associated with specific changes in the neuronal morphology and in the gene-expression profile of the NAc that are effectively reversed after treatment with antidepressants.
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影响因子：
11
作者：
Bessa, J. M.;Ferreira, D.;Sousa, N.
通讯作者：
Sousa, N.
影响因子：
2.4
作者：
Cardinal RN;Cheung TH
通讯作者：
Cheung TH
影响因子：
3
作者：
GLASER, EM;VANDERLOOS, H
通讯作者：
VANDERLOOS, H
DOI：
10.1126/science.1222265
发表时间：
2012-10-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Koo JW;Mazei-Robison MS;Chaudhury D;Juarez B;LaPlant Q;Ferguson D;Feng J;Sun H;Scobie KN;Damez-Werno D;Crumiller M;Ohnishi YN;Ohnishi YH;Mouzon E;Dietz DM;Lobo MK;Neve RL;Russo SJ;Han MH;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
5.3
作者：
Cerqueira, Joao J.;Mailliet, Francois;Sousa, Nuno
通讯作者：
Sousa, Nuno