title: Corticosterone regulates fear memory via Rac1 activity in the hippocampus.
abstract: Stressful events can generate enduring memories, which may induce certain psychiatric disorders such as post-traumatic stress disorder (PTSD). However, the underlying molecular mechanisms in these processes remain unclear. In this study, we examined whether the active form of the small G protein Rac1, Rac1-GTP, is involved in fear memory. Firstly, we detected the time course changes of Rac1-GTP after foot shocks (a strong stressor) and exogenous corticosterone (CORT) treatment. The data showed that stress and CORT induced the downregulation of Rac1-GTP in the hippocampus. Changes in the serum CORT level were negatively correlated with the level of Rac1-GTP. Additionally, a glucocorticoid receptor antagonist, RU38486, not only recovered the expression of Rac1-GTP but also impaired fear memory. Furthermore, systemic administration of NSC23766, an inhibitor of Rac1-GTP, improved fear memory at 1.5 and 24h. Therefore, Rac1 activity plays a critical role in stress-related cognition and may be a potential target in stress-related disorders.
authors.affiliation: College of Life Sciences, Yunnan University, China; College of Basic Medicine, Kunming Medical University, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Ze-Yang
authors.initials: ZY
authors.lastname: Ding
authors.affiliation: Endocrinology Department, Second Affiliated Hospital, Kunming Medical University, Kunming, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Gan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Mao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China; CAS Center for Excellence in Brain Science, 320 Yue Yang Road, Shanghai, 200031, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China. Electronic address: quxin_zhou@126.com.
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: D011965:Receptors, Glucocorticoid; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D003345:Corticosterone
keywords: Corticosterone; Fear memory; Foot shocks; Hippocampus; Rac1-GTP; Stress