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MicroRNA134 of Ventral Hippocampus Is Involved in Cocaine Extinction-Induced Anxiety-like and Depression-like Behaviors in Mice.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.omtn.2019.12.030
Yuehan Li 1 , Xue Lu 2 , Jiaxun Nie 2 , Panpan Hu 3 , Feifei Ge 1 , Ti-Fei Yuan 4 , Xiaowei Guan 1
Affiliation  

We previously found that cocaine abuse could increase microRNA134 (miR134) levels in the hippocampus; yet the roles of miR134 in cocaine-related abnormal psychiatric outcomes remain unknown. In this study, using the cocaine-induced conditioned place preference (CPP) mice model, we found that mice exhibit enhanced anxiety-like and depression-like behaviors during the cocaine extinction (CE) period of CPP, accompanied by obviously increased miR134 levels and decreased levels of 19 genes that are associated with synaptic plasticity, glia activity, and neurochemical microenvironments, in the ventral hippocampus (vHP). Knockdown of miR134 in vHP in vivo reversed the changes in 15 of 19 potential gene targets of miR134 and rescued the abnormal anxiety-like and depression-like behavioral outcomes in CE mice. In parallel, knockdown of miR134 reversed CE-induced changes in dendritic spines and synaptic proteins and increased the field excitatory postsynaptic potential (fEPSP) of CA1 pyramidal neurons in the vHP of CE mice. In addition, knockdown of miR134 suppressed the CE-enhanced microglia activity, inflammatory, apoptotic, and oxidative stress statuses in the vHP. With the data taken together, miR134 may be involved in cocaine-associated psychiatric problems, potentially via regulating the expressions of its gene targets that are related to synaptic plasticity and neurochemical microenvironments.



中文翻译:

海马腹侧的MicroRNA134参与可卡因灭绝诱导的小鼠焦虑和抑郁样行为。

我们先前发现滥用可卡因可能会增加海马中的microRNA134(miR134)水平。然而,miR134在可卡因相关的异常精神病学预后中的作用仍然未知。在这项研究中,使用可卡因诱发的条件性位置偏爱(CPP)小鼠模型,我们发现小鼠在CPP的可卡因灭绝(CE)期间表现出增强的焦虑样和抑郁样行为,并伴随着miR134水平和腹侧海马(vHP)中与突触可塑性,神经胶质活动和神经化学微环境有关的19个基因的水平降低。体内vHP中miR134的敲低逆转了miR134的19个潜在基因靶标中15个的变化,并挽救了CE小鼠异常的焦虑样和抑郁样行为行为。同时,敲除miR134可逆转CE诱导的树突棘和突触蛋白的变化,并增加CE小鼠vHP中CA1锥体神经元的场兴奋性突触后突触电位(fEPSP)。此外,敲低miR134可以抑制vHP中CE增强的小胶质细胞活性,炎症,凋亡和氧化应激状态。结合数据,miR134可能参与可卡因相关的精神疾病,可能是通过调节其与突触可塑性和神经化学微环境有关的基因靶标的表达来实现的。

更新日期:2020-01-10
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