Role of microRNA-132 and Mecp2 in methamphetamine dependence
- Author:
Zhen-Jin SHI
1
;
Rui-Lin ZHANG
1
;
Yi-Hang WANG
1
;
Gen-Meng YANG
1
;
Bao-Yu SHEN
1
;
Shang WANG
1
;
Peng-Liang LIU
1
;
Li-Hua LI
1
;
Dong-Xian ZHANG
1
;
Shi-Jun HONG
1
;
Zhen-Jin SHI
2
;
Ya-Mei WU
2
;
Ya-Mei WU
3
;
Ting-Na ZHU
3
;
Yong-Na ZHAO
3
Author Information
- Publication Type:Journal Article
- Keywords: cAMP-response element binding protein(CREB); drug dependence; gene expression; methamphetamine; methyl CpG binding protein 2(Mecp2); miRNA-132
- From: Chinese Pharmacological Bulletin 2022;38(1):73-78
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.
