Effect and mechanism of suberoylanilide hydroxamic acid on fear extinction in mice with chronic so-cial defeat stress
10.3760/cma.j.issn.1674-6554.2019.08.010
- VernacularTitle:组蛋白去乙酰化酶抑制剂对慢性社交挫败应激小鼠恐惧记忆消退的影响及作用机制
- Author:
Han GAO
1
;
Luoyue YIN
;
Qikai TANG
;
Hanbing XU
;
Shenshen GAO
;
Jingru HAO
;
Can GAO
Author Information
1. 徐州医科大学江苏省麻醉学重点实验室(江苏省麻醉与镇痛应用技术重点实验室) 221004
- Keywords:
Suberoylanilide hydroxamic acid,histone deacetylases inhibitor;
Brain-derived neuro-trophic factor;
Chronic stress;
Fear extinction;
Social defeat
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2019;28(8):721-726
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of suberoylanilide hydroxamic acid (SAHA) on the fear extinction in mice with chronic social defeat stress (SD). Methods Fifty-six male C57BL/6J mice aged 7-8 weeks were randomly divided into control group,social defeat group,control-SAHA group and social defeat-SAHA group to investigate the effect of SAHA and social defeat group,social defeat-AAV BDNF group and social defeat-AAV blank group to investigate the effect of BDNF. Fear extinction in mice was evaluated by fear conditioning test (FC). The levels of BDNF and HDAC2 in mice hippocampus were detected by Western blot (WB). The expression of BDNF-overexpressing virus in hippocampus of mice was detected by immunofluorescence assay. Results (1) Compared with control group,fear extinction in the social defeat group was significantly decreased (P<0. 05). Compared with control group, the level of HDAC2(0. 50±0. 02) in the social defeat group was significantly increased (P<0. 001),while the level of BDNF(0. 16 ± 0. 03) was significantly decreased (P<0. 001) in the social defeat group. ( 2) After using SAHA,fear extinction of mice significantly improved (P<0. 05). Compared with control group,the level of HDAC2 (0. 26±0. 02) in the control-SAHA group was significantly decreased(P<0. 001),and the level of BDNF (0. 40±0. 03) was significantly increased (P<0. 001). Compared with social defeat group,the level of HDAC2 (0. 39±0. 03) in the social defeat-SAHA group was significantly decreased (P<0. 001),and the lev-el of BDNF (0. 28±0. 01) was significantly increased (P<0. 001). (3)After injection BDNF-overexpressing virus,fear extinction was significantly improved(P<0. 05). Conclusion SAHA can enhance fear extinction in mice with chronic social defeat stress and its mechanism may be related to the up-regulation of BDNF ex-pression in hippocampus by inhibiting HDAC2 in hippocampal.
