TY - JOUR
T1 - Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice
AU - Okamura, Hibiki
AU - Yasugaki, Shinnosuke
AU - Suzuki-Abe, Haruka
AU - Arai, Yoshifumi
AU - Sakurai, Katsuyasu
AU - Yanagisawa, Masashi
AU - Takizawa, Hotaka
AU - Hayashi, Yu
N1 - Funding Information:
This work was supported by Japan Society for the Promotion of Science (JSPS) Grants JP20H03353, JP20J21209, and JP20K21456; the Ministry of Education, Culture, Sports, Science and Technology Grant JP21H00199; Japan Agency for Medical Research and Development (AMED) Grants JP19gm1110008 and JP21wm0425018; the Astellas Foundation for Research on Metabolic Disorders; the Daiichi Sankyo Foundation of Life Science; the Asahi Glass Foundation (AGF); the Tanuma Green House Foundation; and the Kao Foundation for Research on Health Science.
Publisher Copyright:
© 2022 Okamura et al.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Understanding the long-term effects of stress on brain function is crucial for understanding the mechanisms of depression. The BALB/c mouse strain has high susceptibility to stress and is thus an effective model for depression. The long-term effects of repeated social defeat stress (SDS) on BALB/c mice, however, are not clear. Here, we investigated the effects of repeated SDS in male BALB/c mice over the subsequent two weeks. Some defeated mice immediately exhibited social avoidance, whereas anxiety-like behavior was only evident at later periods. Furthermore, defeated mice segregated into two groups based on the level of social avoidance, namely, avoidant and nonavoidant mice. The characteristic of avoidance or nonavoidance in each individual was not fixed over the two weeks. In addition, we developed a semi-automated method for analyzing c-Fos expression in the mouse brain to investigate the effect of repeated SDS on brain activity more than two weeks after the end of the stress exposure. Following social interaction, c-Fos expression was reduced in several brain regions in the defeated mice compared with control mice. The correlation of c-Fos expression among these brain areas, with exception of the medial prefrontal cortex (mPFC) and central amygdala (CeA), was increased in defeated mice, suggesting increased synchrony. Notably, c-Fos expression in the lateral habenula (LHb) was different between mice that exhibited social avoidance from immediately after the repeated SDS and those that exhibited social avoidance only at later periods. These observations provide insight into the long-term effects of social stress on behavior and brain activity.
AB - Understanding the long-term effects of stress on brain function is crucial for understanding the mechanisms of depression. The BALB/c mouse strain has high susceptibility to stress and is thus an effective model for depression. The long-term effects of repeated social defeat stress (SDS) on BALB/c mice, however, are not clear. Here, we investigated the effects of repeated SDS in male BALB/c mice over the subsequent two weeks. Some defeated mice immediately exhibited social avoidance, whereas anxiety-like behavior was only evident at later periods. Furthermore, defeated mice segregated into two groups based on the level of social avoidance, namely, avoidant and nonavoidant mice. The characteristic of avoidance or nonavoidance in each individual was not fixed over the two weeks. In addition, we developed a semi-automated method for analyzing c-Fos expression in the mouse brain to investigate the effect of repeated SDS on brain activity more than two weeks after the end of the stress exposure. Following social interaction, c-Fos expression was reduced in several brain regions in the defeated mice compared with control mice. The correlation of c-Fos expression among these brain areas, with exception of the medial prefrontal cortex (mPFC) and central amygdala (CeA), was increased in defeated mice, suggesting increased synchrony. Notably, c-Fos expression in the lateral habenula (LHb) was different between mice that exhibited social avoidance from immediately after the repeated SDS and those that exhibited social avoidance only at later periods. These observations provide insight into the long-term effects of social stress on behavior and brain activity.
KW - c-Fos
KW - stress
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U2 - 10.1523/ENEURO.0068-22.2022
DO - 10.1523/ENEURO.0068-22.2022
M3 - Article
C2 - 35437264
AN - SCOPUS:85129382893
SN - 2373-2822
VL - 9
JO - eNeuro
JF - eNeuro
IS - 3
M1 - ENEURO.0068-22.2022
ER -