Mitophagy in the basolateral amygdala mediates increased anxiety induced by aversive social experience

Psychosocial stress is a common risk factor for anxiety disorders. The cellular mechanism for the anxiogenic effect of psychosocial stress is largely unclear. Here, we show that chronic social defeat (CSD) stress in mice causes mitochondrial impairment, which triggers the PINK1-Parkin mitophagy path...

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Veröffentlicht in:Neuron (Cambridge, Mass.) Mass.), 2021-12, Vol.109 (23), p.3793-3809.e8
Hauptverfasser: Duan, Kaizheng, Gu, Qinhua, Petralia, Ronald S., Wang, Ya-Xian, Panja, Debabrata, Liu, Xing, Lehmann, Michael L., Zhu, Huiwen, Zhu, Jun, Li, Zheng
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Sprache:eng
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Zusammenfassung:Psychosocial stress is a common risk factor for anxiety disorders. The cellular mechanism for the anxiogenic effect of psychosocial stress is largely unclear. Here, we show that chronic social defeat (CSD) stress in mice causes mitochondrial impairment, which triggers the PINK1-Parkin mitophagy pathway selectively in the amygdala. This mitophagy elevation causes excessive mitochondrial elimination and consequent mitochondrial deficiency. Mitochondrial deficiency in the basolateral amygdalae (BLA) causes weakening of synaptic transmission in the BLA-BNST (bed nucleus of the stria terminalis) anxiolytic pathway and increased anxiety. The CSD-induced increase in anxiety-like behaviors is abolished in Pink1−/− and Park2−/− mice and alleviated by optogenetic activation of the BLA-BNST synapse. This study identifies an unsuspected role of mitophagy in psychogenetic-stress-induced anxiety elevation and reveals that mitochondrial deficiency is sufficient to increase anxiety and underlies the psychosocial-stress-induced anxiety increase. Mitochondria and mitophagy, therefore, can be potentially targeted to ameliorate anxiety. [Display omitted] •Mitochondria in the amygdala are impaired by chronic social defeat stress•Damaged mitochondria trigger mitophagy•Elevated mitophagy causes excessive mitochondrial elimination•Mitochondrial loss induces weakening of synapses in the BLA-BNST anxiolytic pathway Duan et al. reveal a key role of mitophagy in anxiety induced by chronic psychogenic stress. Mitophagy is enhanced by stress to cause mitochondrial loss, leading to synaptic weakening in the anxiolytic pathway mediated by the extended amygdala. Mitochondria and mitophagy, therefore, may be targeted to ameliorate anxiety.
ISSN:0896-6273
1097-4199
1097-4199
DOI:10.1016/j.neuron.2021.09.008