Corticosterone regulates fear memory via Rac1 activity in the hippocampus

Ping Gan; Ze-Yang Ding; Cheng Gan; Rong-Rong Mao; Heng Zhou; Lin Xu; Qi-Xin Zhou

doi:10.1016/j.psyneuen.2016.05.011

Corticosterone regulates fear memory via Rac1 activity in the hippocampus

Psychoneuroendocrinology. 2016 Sep:71:86-93. doi: 10.1016/j.psyneuen.2016.05.011. Epub 2016 May 18.

Authors

Ping Gan¹, Ze-Yang Ding², Cheng Gan³, Rong-Rong Mao², Heng Zhou², Lin Xu⁴, Qi-Xin Zhou⁵

Affiliations

¹ 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.
² 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.
³ Endocrinology Department, Second Affiliated Hospital, Kunming Medical University, Kunming, China.
⁴ 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.
⁵ 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.

PMID: 27249795
DOI: 10.1016/j.psyneuen.2016.05.011

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.

Keywords: Corticosterone; Fear memory; Foot shocks; Hippocampus; Rac1-GTP; Stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Corticosterone / blood
Corticosterone / metabolism*
Fear / drug effects
Fear / physiology*
Fear / psychology
Hippocampus / metabolism
Male
Memory / drug effects
Memory / physiology
Memory Disorders / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid / metabolism
Stress, Psychological / metabolism
rac1 GTP-Binding Protein / genetics
rac1 GTP-Binding Protein / metabolism*
rac1 GTP-Binding Protein / physiology*

Substances

Receptors, Glucocorticoid
Rac1 protein, rat
rac1 GTP-Binding Protein
Corticosterone

Grants and funding

CIHR/Canada