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条件性抑制成体神经发生通过诱导和靶向 ERK5 MAP 激酶缺失与焦虑/抑郁样行为无关。

Conditional Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 MAP Kinase Is Not Associated with Anxiety/Depression-Like Behaviors.

机构信息

Toxicology Program in the Department of Environmental and Occupational Health Sciences.

Department of Pharmacology, University of Washington , Seattle, Washington 98195.

出版信息

eNeuro. 2015 Apr 16;2(2). doi: 10.1523/ENEURO.0014-14.2015. eCollection 2015 Mar-Apr.

Abstract

Although there is evidence that adult neurogenesis contributes to the therapeutic efficacy of chronic antidepressant treatment for anxiety and depression disorders, the role of adult neurogenesis in the onset of depression-related symptoms is still open to question. To address this issue, we utilized a transgenic mouse strain in which adult neurogenesis was specifically and conditionally impaired by Nestin-CreER-driven, inducible knockout (icKO) of erk5 MAP kinase in Nestin-expressing neural progenitors of the adult mouse brain upon tamoxifen administration. Here, we report that inhibition of adult neurogenesis by this mechanism is not associated with an increase of the baseline anxiety or depression in non-stressed animals, nor does it increase the animal's susceptibility to depression after chronic unpredictable stress treatment. Our findings indicate that impaired adult neurogenesis does not lead to anxiety or depression.

摘要

虽然有证据表明,成年神经发生有助于慢性抗抑郁治疗焦虑和抑郁障碍的疗效,但成年神经发生在抑郁相关症状的发生中的作用仍存在争议。为了解决这个问题,我们利用了一种转基因小鼠品系,其中成年神经发生通过 Nestin-CreER 驱动的、在成年小鼠脑中巢蛋白表达的神经祖细胞中诱导性敲除(icKO)erk5 MAP 激酶而被特异性且条件性地破坏,在给予他莫昔芬时。在这里,我们报告说,通过这种机制抑制成年神经发生与非应激动物基线焦虑或抑郁的增加无关,也不会增加动物在慢性不可预测应激处理后的易感性。我们的研究结果表明,成年神经发生受损不会导致焦虑或抑郁。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9823/4596085/0187bfd1250c/enu0021500720001.jpg

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