Uncovering the cellular causes of anxiety due to social stress



Humans and other animals alike experience anxiety due to social stress, and anxiety disorders comprise the most common mental health disorder in the U.S. Previous studies have shown links among stress, behavior, and mitochondria, the chemical powerplants inside cells. However, the effects of social stress on the brain at the cellular level remain unknown, and until now, it has been unclear whether mitochondrial disturbances are a cause or effect of behavioral changes associated with stress.


Researchers led by IRP senior investigator Zheng Li, Ph.D., examined how social stress caused by repeated exposure to an aggressor affects mitochondria in the brains of mice. The research team focused on the amygdala, a brain region involved in processing fearful and threatening experiences, and the hippocampus, a part of the brain involved in the stress response and emotional reactions. Mice repeatedly exposed to aggressor mice showed signs of stress after the experiences ended, and the rate of mitophagy — the selective destruction of mitochondria — in the amygdala increased. The resulting decrease in numbers of mitochondria in the amygdala weakened communication between neurons in a brain pathway controlling anxiety.


In discovering that anxiety-like behavior is linked to loss of mitochondria in the amygdala in mice and identifying the specific cellular mechanisms involved, the researchers have identified and described a key mechanism underlying anxiety and identified new potential targets for therapies to alleviate anxiety disorders.


Kaizheng Duan, Qinhua Gu, Ronald S. Petralia, Ya-Xian Wang, Debabrata Panja, Xing Liu, Michael L. Lehmann, Huiwen Zhu, Jun Zhu, Zheng Li. (2021). Mitophagy in the basolateral amygdala mediates increased anxiety induced by aversive social experience. Neuron. 109(23):3793-3809.e8. doi: 10.1016/j.neuron.2021.09.008.

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This page was last updated on Thursday, June 8, 2023