2. Academic Validation
  3. 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

  • Neuropharmacology. 2021 Feb 15;184:108410. doi: 10.1016/j.neuropharm.2020.108410.
Yan-Hui Cui 1,  Ao Fu 2,  Xue-Qin Wang 3,  Bo-Xuan Tu 4,  Kang-Zhi Chen 5,  Yi-Kai Wang 5,  Qiong-Gui Hu 5,  Lai-Fa Wang 3,  Zhao-Lan Hu 6,  Pin-Hua Pan 7,  Fang Li 4,  Fang-Fang Bi 8,  Chang-Qi Li 9
Affiliations

Affiliations

  • 1 Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, 410013, China; Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
  • 2 Clinic Medicine of 5-year Program, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
  • 3 Center for Neuroscience and behavior, Changsha Medical University, Changsha, 410219, China.
  • 4 Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, 410013, China.
  • 5 Clinic Medicine of 8-year Program, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
  • 6 Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
  • 7 Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
  • 8 Department of Neurology, XiangYa Hospital, Central South University, Changsha, 410008, China. Electronic address: fangfangbi@csu.edu.cn.
  • 9 Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, 410013, China. Electronic address: changqili@csu.edu.cn.
PMID: 33242526 DOI: 10.1016/j.neuropharm.2020.108410
Abstract

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.

Keywords

AKT; Antidepressant; Depression; Hippocampus; LASP1.

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