Disinhibition of somatostatin interneurons confers resilience to stress in male but not female mice.
Disinhibition of somatostatin interneurons confers resilience to stress in male but not female mice.
复制标题
生长抑素中间神经元的去抑制可以赋予雄性小鼠而非雌性小鼠的压力恢复能力。
DOI：
10.1016/j.ynstr.2020.100238
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发表时间：
2020-11
影响因子：
5
通讯作者：
Luscher B
中科院分区：
文献类型：
--
作者：
Jefferson SJ;Feng M;Chon U;Guo Y;Kim Y;Luscher B
慢性压力是焦虑和抑郁障碍的一个脆弱因素，并已被广泛用于啮齿动物中这些疾病的建模。通过选择性地从这些细胞（SSTCre:γ2f/f小鼠）中删除γ - 2 GABAA受体来解除对小鼠生长抑素（SST）阳性gaba能中间神经元的抑制作用，已被证明会导致行为和生化变化，类似于抗抑郁剂量氯胺酮的反应。在这里，我们探讨了SSTCre:γ2f/f小鼠对不可预测的慢性轻度应激（UCMS）表现出弹性的程度。我们发现雄性SSTCre:γ2f/f小鼠对ucms诱导的(i)体重增加减少，（ii）内侧前额叶皮层（mPFC）中sst免疫阳性细胞减少，（iii） mPFC中真核延伸因子2 （eEF2）磷酸化增加，以及（iv）新颖性抑制喂养试验中焦虑增加。雌性sstre:γ2f/f小鼠对ucms诱导的sst免疫阳性细胞减少具有弹性，与雄性小鼠无明显区别。然而，与男性相比，他们没有显示出独立于基因型的UCMS对体重增加的影响。此外，在雌性γ2f/f对照小鼠的mPFC中，UCMS导致sstre:γ2f/f突变体中p-EF2水平的矛盾降低，而没有应激效应。最后，与γ2f/f对照相比，雌性SSTCre:γ2f/f小鼠显示出UCMS诱导的焦虑增加而不是减少。因此，SST中间神经元的去抑制导致雄性小鼠选择性地对UCMS具有行为弹性，同时SST神经元对UCMS具有独立于性别的细胞弹性。因此，对压力的脆弱性和恢复力的机制是性别特异性的，映射到mPFC而不是海马，但似乎与作为相应中间神经元标记的SST表达的变化无关。
Chronic stress represents a vulnerability factor for anxiety and depressive disorders and has been widely used to model aspects of these disorders in rodents. Disinhibition of somatostatin (SST)-positive GABAergic interneurons in mice by deletion of γ2 GABAA receptors selectively from these cells (SSTCre:γ2f/f mice) has been shown to result in behavioral and biochemical changes that mimic the responses to antidepressant doses of ketamine. Here we explored the extent to which SSTCre:γ2f/f mice exhibit resilience to unpredictable chronic mild stress (UCMS). We found that male SSTCre:γ2f/f mice are resilient to UCMS-induced (i) reductions in weight gain, (ii) reductions in SST-immuno-positive cells in medial prefrontal cortex (mPFC), (iii) increases in phosphorylation of eukaryotic elongation factor 2 (eEF2) in mPFC, and (iv) increased anxiety in a novelty suppressed feeding test. Female SSTCre:γ2f/f mice were resilient to UCMS-induced reductions in SST-immuno-positive cells indistinguishably from males. However, in contrast to males, they showed no UCMS effects on weight gain independent of genotype. Moreover, in mPFC of female γ2f/f control mice, UCMS resulted in paradoxically reduced p-EF2 levels without stress effects in the SSTCre:γ2f/f mutants. Lastly, female SSTCre:γ2f/f mice showed increased rather than reduced UCMS induced anxiety compared to γ2f/f controls. Thus, disinhibition of SST interneurons results in behavioral resilience to UCMS selectively in male mice, along with cellular resilience of SST neurons to UCMS independent of sex. Thus, mechanisms underlying vulnerability and resilience to stress are sex specific and map to mPFC rather than hippocampus but appear unrelated to changes in expression of SST as a marker of corresponding interneurons.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
生长抑素，神经元脆弱性和行为情绪。
影响因子：
11
作者：
Lin, L. C.;Sibille, E.
通讯作者：
Sibille, E.
小鼠大脑皮层 GABA 神经元组合靶向的策略和工具
影响因子：
16.2
作者：
He M;Tucciarone J;Lee S;Nigro MJ;Kim Y;Levine JM;Kelly SM;Krugikov I;Wu P;Chen Y;Gong L;Hou Y;Osten P;Rudy B;Huang ZJ
通讯作者：
Huang ZJ
影响因子：
5.3
作者：
Earnheart, John C.;Schweizer, Claude;Luscher, Bernhard
通讯作者：
Luscher, Bernhard
影响因子：
25
作者：
Essrich, C;Lorez, M;Lüscher, B
通讯作者：
Lüscher, B