Gene-environment interactions mediate stress susceptibility and resilience through the CaMKIIβ/TARPγ-8/AMPAR pathway.
Gene-environment interactions mediate stress susceptibility and resilience through the CaMKIIβ/TARPγ-8/AMPAR pathway.
复制标题
DOI：
10.1016/j.isci.2021.102504
复制
发表时间：
2021-05-21
期刊：
影响因子：
5.8
通讯作者：
Uchida S
中科院分区：
文献类型：
--
作者：
Sakai Y;Li H;Inaba H;Funayama Y;Ishimori E;Kawatake-Kuno A;Yamagata H;Seki T;Hobara T;Nakagawa S;Watanabe Y;Tomita S;Murai T;Uchida S
虽然压力事件使个体易患精神疾病，如抑郁症，但并不是所有经历压力生活经历的人都会抑郁，这表明基因-环境相互作用（GxE）决定了抑郁症的风险。腹侧海马（vHPC）在动机，社交，快感缺乏，绝望样行为，焦虑，睡眠和进食中起着关键作用，这表明该大脑区域参与了抑郁症。然而，vHPC和GxE之间在塑造行为易感性和对慢性压力的恢复力方面的相互作用的分子机制仍然难以捉摸。在这里，我们发现，在抑郁易感性和恢复力的GxE小鼠模型中，vHPC中的Ca 2 +/钙调素依赖性蛋白激酶IIβ（CaMKIIβ）活性受到差异调节，CaMKIIβ介导的TARPγ-8磷酸化增强了突触后位点AMPA受体亚基GluA 1的表达，从而实现应激恢复力。我们提出了以前缺失的慢性应激引起的行为变化的分子机制，为预防和治疗应激相关的精神疾病提供了策略。在抑郁/恢复力GxE模型中，CaMKII β活性受到差异性调节CaMKII β活性对于确定应激易感性和恢复力至关重要CaMKIIβ介导的TARP γ-8激活发挥促恢复力作用TARPγ-8介导的GluA 1突触表达赋予慢性应激恢复力行为神经科学;分子神经科学;细胞神经科学。
Although stressful events predispose individuals to psychiatric disorders, such as depression, not all people who undergo a stressful life experience become depressed, suggesting that gene-environment interactions (GxE) determine depression risk. The ventral hippocampus (vHPC) plays key roles in motivation, sociability, anhedonia, despair-like behaviors, anxiety, sleep, and feeding, pointing to the involvement of this brain region in depression. However, the molecular mechanisms underlying the cross talk between the vHPC and GxE in shaping behavioral susceptibility and resilience to chronic stress remain elusive. Here, we show that Ca2+/calmodulin-dependent protein kinase IIβ (CaMKIIβ) activity in the vHPC is differentially modulated in GxE mouse models of depression susceptibility and resilience, and that CaMKIIβ-mediated TARPγ-8 phosphorylation enhances the expression of AMPA receptor subunit GluA1 in the postsynaptic sites to enable stress resilience. We present previously missing molecular mechanisms underlying chronic stress-elicited behavioral changes, providing strategies for preventing and treating stress-related psychiatric disorders. CaMKIIβ activity is differentially modulated in a depression/resilience GxE model CaMKIIβ activity is critical for determining stress susceptibility and resilience CaMKIIβ-mediated TARPγ-8 activation exerts pro-resilience effects TARPγ-8-mediated synaptic expression of GluA1 confers chronic stress resiliency Behavioral neuroscience; Molecular neuroscience; Cellular neuroscience.
登录
查看更多内容
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.
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
64.8
作者：
Hovatta, I;Tennant, RS;Barlow, C
通讯作者：
Barlow, C
DOI：
10.1111/j.1749-6632.2012.06669.x
发表时间：
2012-01-01
期刊：
BRAIN STIMULATION IN NEUROLOGY AND PSYCHIATRY
影响因子：
--
作者：
Dzirasa, Kafui;Covington, Herbert E., III
通讯作者：
Covington, Herbert E., III
影响因子：
11
作者：
Carreno, F. R.;Donegan, J. J.;Lodge, D. J.
通讯作者：
Lodge, D. J.