Corticosterone Impairs Hippocampal Neurogenesis and Behaviors through p21 -Mediated ROS Accumulation

• Published in: Biomolecules (Basel, Switzerland) Vol. 14; no. 3; p. 268
• Main Authors: Wang, Guanhao, Cao, Lining, Li, Shuanqing, Zhang, Meihui, Li, Yingqi, Duan, Jinjin, Li, You, Hu, Zhangsen, Wu, Jiaan, Li, Tianming, Jiang, Ming, Lu, Jianfeng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.02.2024; MDPI
• Subjects: Antioxidants; Anxiety; Anxiety disorders; anxiety-like behaviors; Atrophy; Behavior; Brain; Chronic illnesses; Corticosterone; Corticosterone - metabolism; Corticosterone - pharmacology; Cyclin-dependent kinase inhibitor p21; Dentate gyrus; Depression - drug therapy; Generalized anxiety disorder; Hippocampus; Hippocampus - metabolism; Hormones; Neurogenesis; Neurogenesis - physiology; Oxidative stress; p21; Phenotypes; Reactive Oxygen Species; Stress; United States > US; China; neurogenesis; anxiety-like behaviors; corticosterone; p21
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14030268

Stress is known to induce a reduction in adult hippocampal neurogenesis (AHN) and anxiety-like behaviors. Glucocorticoids (GCs) are secreted in response to stress, and the hippocampus possesses the greatest levels of GC receptors, highlighting the potential of GCs in mediating stress-induced hippocampal alterations and behavior deficits. Herein, RNA-sequencing (RNA-seq) analysis of the hippocampus following corticosterone (CORT) exposure revealed the central regulatory role of the gene, which exhibited interactions with oxidative stress-related differentially expressed genes (DEGs), suggesting a potential link between and oxidative stress-related pathways. Remarkably, -overexpression in the hippocampal dentate gyrus partially recapitulated CORT-induced phenotypes, including reactive oxygen species (ROS) accumulation, diminished AHN, dendritic atrophy, and the onset of anxiety-like behaviors. Significantly, inhibiting ROS exhibited a partial rescue of anxiety-like behaviors and hippocampal alterations induced by -overexpression, as well as those induced by CORT, underscoring the therapeutic potential of targeting ROS or in the hippocampus as a promising avenue for mitigating anxiety disorders provoked by chronic stress.