Vortioxetine attenuates the effects of early-life stress on depression-like behaviors and monoamine transporters in female mice
Vortioxetine attenuates the effects of early-life stress on depression-like behaviors and monoamine transporters in female mice
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沃替西汀减轻早期生活压力对雌性小鼠抑郁样行为和单胺转运蛋白的影响
DOI：
10.1016/j.neuropharm.2021.108468
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发表时间：
2021-01-27
影响因子：
4.7
通讯作者：
Si，Tian-Mei
中科院分区：
文献类型：
--
作者：
Liu，Xiao;Sun，Ya-Xin;Si，Tian-Mei
重度抑郁症是一种严重的精神疾病，也是全世界致残的主要原因。女性患抑郁症的几率大约是男性的两倍。然而，抑郁症的临床前动物模型很少研究与女性较高抑郁风险相关的分子改变。在本研究中，采用有限的床上用品和筑巢材料的早期生活应激（ELS）范式，我们发现ELS仅在成年雌性小鼠中诱导抑郁样行为，并通过蔗糖偏好和悬尾测试进行了评估。然后，我们检测了ELS对雌性小鼠抑郁相关脑区单胺神经传递（单胺再摄取和释放的转运体）的影响。我们发现ELS导致这些转运蛋白在四个脑区表达水平的广泛改变。此外，用沃替西汀（一种新型多模式抗抑郁药）系统治疗21天，成功逆转了抑郁样行为，并使一些分子变化正常化，包括内侧前额叶皮层的去甲肾上腺素转运蛋白、伏隔核核的单胺转运蛋白2和杏仁核的血清素转运蛋白。总的来说，这些结果为使用有限的被褥和筑巢材料范式来研究抑郁症的性别差异提供了证据，并证明了单胺神经传递的区域特异性改变可能与雌性小鼠的抑郁样行为有关。这篇文章是“压力、成瘾和可塑性”特刊的一部分。
Major depressive disorder is a major psychiatric disorder and a leading cause of disability around the world. Females have about twice as high an incidence of depression as males. However, preclinical animal models of depression have seldom investigated the molecular alterations associated with higher depression risk in females. In this study, adopting the early-life stress (ELS) paradigm of limited bedding and nesting material, we found that ELS induced depression-like behaviors only in adult female mice, as evaluated by sucrose preference and tail suspension tests. We then examined the ELS effects on monoamine neurotransmission (transporters for monoamine reuptake and release) in depression-related brain regions in female mice. We found that ELS resulted in widespread changes of the expression levels of these transporters in four brain regions. Moreover, systemic 21-day treatment with vortioxetine, a novel multimodal antidepressant, successfully reversed depression-like behaviors and normalized some molecular changes, including that of the norepinephrine transporter in the medial prefrontal cortex, vesicular monoamine transporter 2 in nucleus accumbens core, and serotonin transporter in amygdala. Collectively, these results provide evidence for the validity of using the limited bedding and nesting material paradigm to investigate sex differences in depression and demonstrate that the region-specific alterations of monoamine neurotransmission may be associated with depression-like behaviors in female mice.This article is part of the special issue on ‘Stress, Addiction and Plasticity’.