From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress.
From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress.
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从压力到抑郁：社会压力后细胞外基质依赖性认知障碍的发展。
DOI：
10.1038/s41598-020-73173-2
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发表时间：
2020-10-14
影响因子：
4.6
通讯作者：
Spijker S
中科院分区：
文献类型：
--
作者：
Koskinen MK;van Mourik Y;Smit AB;Riga D;Spijker S
压力可以诱发抑郁发作，但从最初的压力反应到持续的病理性抑郁状态的分子机制仍然知之甚少。我们通过评估社交失败压力后2个月内的情感行为和海马功能，描述了持久抑郁样状态的发展。在此期间，我们测量了海马细胞外基质（ECM）的重塑，因为我们最近发现ECM的变化介导了持续抑郁样状态下的认知障碍。社会应激后，情感障碍和认知障碍会随之发展，并逐渐出现情感缺陷。相比之下，空间记忆受损后的早期压力和后期出现的慢性抑郁样状态，而完整的之间。同样，我们观察到海马ECM的双相调节与海马依赖性记忆缺陷相一致。总之，我们的数据（1）揭示了情感和认知障碍之间的二分法，类似于在患者中观察到的，（2）表明在早期应激和慢性抑郁样状态期间发生的不同分子过程，（3）支持ECM在介导对记忆的长期影响中的作用。从翻译的角度来看，重要的是优先考虑在动物模型中的时间表型方面，以阐明抑郁症的潜在机制。
Stress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. We profiled the development of an enduring depressive-like state by assessing affective behavior and hippocampal function during the 2 months following social-defeat stress. We measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM changes to mediate cognitive impairment during the sustained depressive-like state. Affective disturbance and cognitive impairments develop disparately after social stress, with gradual appearance of affective deficits. In contrast, spatial memory was impaired both early after stress and during the late-emerging chronic depressive-like state, while intact in-between. Similarly, we observed a biphasic regulation of the hippocampal ECM coinciding with hippocampus-dependent memory deficits. Together our data (1) reveal a dichotomy between affective and cognitive impairments similar to that observed in patients, (2) indicate different molecular processes taking place during early stress and the chronic depressive-like state, and (3) support a role of the ECM in mediating long-lasting effects on memory. From a translational point of view, it is important to prioritize on temporal phenotypic aspects in animal models to elucidate the underlying mechanisms of depression.
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影响因子：
2.9
作者：
Ferrer-Ferrer M;Dityatev A
通讯作者：
Dityatev A
影响因子：
3
作者：
Dityatev, Alexander;Brueckner, Gert;Schachner, Melitta
通讯作者：
Schachner, Melitta
影响因子：
2.2
作者：
Douglas, LA;Varlinskaya, EI;Spear, LP
通讯作者：
Spear, LP
DOI：
10.1097/01.jgp.0000203130.45421.69
发表时间：
2006-05-01
影响因子：
7.2
作者：
Bhalla, RK;Butters, MA;Becker, JT
通讯作者：
Becker, JT
影响因子：
5
作者：
Aguayo, Felipe I.;Pacheco, Anibal A.;Fiedler, Jenny L.
通讯作者：
Fiedler, Jenny L.