Hippocampal LASP1 ameliorates chronic stress-mediated behavioral responses in a mouse model of unpredictable chronic mild stress
Hippocampal LASP1 ameliorates chronic stress-mediated behavioral responses in a mouse model of unpredictable chronic mild stress
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海马 LASP1 改善不可预测的慢性轻度应激小鼠模型中慢性应激介导的行为反应
DOI：
10.1016/j.neuropharm.2020.108410
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发表时间：
2021-02-15
影响因子：
4.7
通讯作者：
Li, Chang-Qi
中科院分区：
文献类型：
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作者：
Cui, Yan-Hui;Fu, Ao;Li, Chang-Qi
大量证据表明，突触可塑性异常在抑郁症的发病过程中起着重要作用。LASP1(LIM和SH3结构域蛋白1)是肌动蛋白结合蛋白的一员，已被证明与突触可塑性的调节有关。然而，LASP1在情绪调节中的作用尚不清楚。在这里，使用不可预测的慢性温和应激(UCMS)范式，我们发现应激小鼠海马区LASP1的mRNA和蛋白水平降低，长期服用氟西汀可取消UCMS诱导的LASP1下调。腺苷相关病毒介导的海马区LASP1过表达可减轻UCMS诱导的应激小鼠强迫游泳实验和蔗糖偏爱实验的行为结果。它还恢复了树突棘密度，提高了AKT(一种丝氨酸/苏氨酸蛋白激酶)、磷酸化AKT、胰岛素样生长因子2和突触后密度蛋白95的水平。这些发现表明，LASP1可以减轻UCMS引起的行为缺陷，这可能是通过增加树突棘密度和激活更多依赖AKT的LASP1信号来介导的，表明LASP1具有抗抑郁作用。
Substantial evidence has revealed that abnormalities in synaptic plasticity play important roles during the process of depression. LASP1 (LIM and SH3 domain protein 1), a member of actin-binding proteins, has been shown to be associated with the regulation of synaptic plasticity. However, the role of LASP1 in the regulation of mood is still unclear. Here, using an unpredictable chronic mild stress (UCMS) paradigm, we found that the mRNA and protein levels of LASP1 were decreased in the hippocampus of stressed mice and that UCMS-induced down-regulation of LASP1 was abolished by chronic administration of fluoxetine. Adenosine-associated virus-mediated hippocampal LASP1 overexpression alleviated the UCMS-induced behavioral results of forced swimming test and sucrose preference test in stressed mice. It also restored the dendritic spine density, elevated the levels of AKT (a serine/threonine protein kinase), phosphorylated-AKT, insulin-like growth factor 2, and postsynaptic density protein 95. These findings suggest that LASP1 alleviates UCMS-provoked behavioral defects, which may be mediated by an enhanced dendritic spine density and more activated AKT-dependent LASP1 signaling, pointing to the antidepressant role of LASP1.