Effect of corticosterone on expression of brain-derived neurotrophic factors in CA1 region of rat hippocampus and its mechanism
10.13200/j.cnki.cjb.004546
- VernacularTitle:皮质酮对大鼠海马CA1区脑源性神经营养因子表达的影响及其作用机制
- Author:
LIU Jialin
- Publication Type:Journal Article
- Keywords:
Corticosterone(CORT);
Depression;
Brain-derived neurotrophic factor(BDNF);
Transcripts;
Histone methylation;
Hippocampus
- From:
Chinese Journal of Biologicals
2025;38(08):913-919
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of corticosterone(CORT) on the expression of brain-derived neurotrophic factors(BDNFs) in the CA1 region of rat hippocampus and its mechanism, so as to provide new ideas for the study of the pathogenesis of depression.Methods A rat model with depressive-like behavior was established by long-term oral administration of CORT, and the control group was set up(no administration). Western blot was used to detect the expression levels of BDNFs and precursor BDNF(proBDNF) in the CA1 region of rat hippocampus. In situ hybridization(ISH) assay was used to detect the expression distribution of Bdnf transcripts Ⅰ、Ⅱ、Ⅳ and Ⅵ in the CA1 region of the hippocampus. Chromatin immunoprecipitation(ChIP) assay was used to detect the trimethylation of histones H3K4, H3K9, H3K27 and H3K36 in the promoters p1, p2, p4 and p6 of Bdnf gene in the CA1 region.Results Compared with the control group, the expression of BDNF protein in the CA1 region of rat hippocampus in the CORT group significantly decreased(t = 2. 842, P < 0. 05),while the expression of proBDNF protein significantly increased(t = 3. 227, P < 0. 05); the expression of Bdnf transcripts Ⅰ,Ⅱ,Ⅳ and Ⅵ decreased; the trimethylation levels of histones H3K4, H3K9, H3K27 and H3K36 in the p1 region of Bdnf promoter significantly increased(t = 17. 280 0, 4. 649 0, 10. 480 0, and 46. 570 0, respectively, each P < 0. 001); there was no significant difference in the trimethylation levels of the four sites in p2 and p4 regions of Bdnf promoter(t = 0. 105 1-2. 633 0, each P > 0. 05); the trimethylation level at H3K27 in the p6 region significantly increased(t = 5. 383 0, P < 0. 018), while there was no significant difference at H3K4, H3K9 and H3K36(t = 2. 022 0, 0. 875 0, 0. 486 2, respectively, each P > 0. 05).Conclusion Oral administration of CORT can induce depression-like behaviors in rats, and cause the significantly decreased expression of BDNF protein and significantly increased expression of proBDNF protein in the CA1 region of rat hippocampus in CORT group, which may be related to the decreased expression of Bdnf transcripts Ⅰ、Ⅱ、Ⅳ and Ⅵ, as well as different histone methylation modification patterns in the p1, p2, p4 and p6 regions of Bdnf promoter.
