2025-03-18 東京大学
<関連情報>
- https://www.s.u-tokyo.ac.jp/ja/info/10719/
- https://www.sciencedirect.com/science/article/pii/S1053811925001193
幼少期の社会的隔離がマウスの脳形態に及ぼす時間および性別依存的影響 Time- and sex-dependent effects of juvenile social isolation on mouse brain morphology
Tatiana Sazhina, Tomokazu Tsurugizawa, Yuki Mochizuki, Aika Saito, Asuka Joji-Nishino, Kazuya Ouchi, Sho Yagishita, Kazuo Emoto, Akira Uematsu
NeuroImage Available online: 4 March 2025
DOI:https://doi.org/10.1016/j.neuroimage.2025.121117
Highlights
- Social isolation affects mouse brain morphology in a time- & sex-dependent manner.
- Juvenile SIS increases several brain regions in female mice.
- Depending on the timing, SIS differentially affects fiber tracts in female mice.
- Early vs late SIS opposingly change distinct brain regions and tracts in male mice.
- SIS leads to context fear generalization in female mice.
Abstract
During early life stages, social isolation disrupts the proper brain growth and brain circuit formation, which is associated with the risk of mental disorders and cognitive deficits in adulthood. Nevertheless, the impact of juvenile social isolation on brain development, particularly regarding variations across age and sex, remains poorly understood. Here, we investigate the effects of social isolation stress (SIS) during early (3-5 weeks old) or late (5-7 weeks old) juvenile period on brain morphology in adult male and female mice using ultra high-field MRI (11.7 T). We found that both early and late SIS in female mice led to volumetric increases in multiple brain regions, such as the medial prefrontal cortex (mPFC) and hippocampus. Correlation tractography revealed that the fiber tracts in the right corpus callosum and right amygdala were positively correlated with SIS in female mice. In male mice, early SIS resulted in small volumetric increases in the isocortex, whereas late SIS led to reductions in the isocortex and hypothalamus. Furthermore, early SIS caused a negative correlation, while late SIS exhibited a positive correlation, with fiber tracts in the corpus callosum and amygdala in male mice. Using a Random Forest classifier, we achieved effective discrimination between socially isolated and control conditions in the brain volume of female mice, with the limbic areas playing a key role in the model’s accuracy. Finally, we discovered that SIS led to context fear generalization in a sex-dependent manner. Our findings highlight the importance of considering both the time- and sex-dependent effects of juvenile SIS on brain development and emotional processing, providing new insights into its long-term consequences.
