Effects of Ppp1r17 down-regulation on drinking-related behaviors and AKT/GSK-3β/CREB signaling pathway activation in mice
10.3969/j.issn.1000-4718.2024.11.001
- VernacularTitle:下调Ppp1r17对小鼠饮酒相关行为及AKT/GSK-3β/CREB信号通路磷酸化的影响
- Author:
Zhuanfang YANG
1
,
2
;
Jiajia HU
;
Xizhe SUN
;
Yan CHENG
;
Juanjuan YUAN
;
Yu ZHANG
;
Litian YIN
Author Information
1. 山西医科大学基础医学院生理学系,细胞生理学教育部重点实验室,山西 太原 030001
2. 国药同煤总医院病理科,山西 大同 037001
- Keywords:
alcohol dependence;
protein phosphatase 1 regulator subunit 17;
hippocampus;
AKT/GSK-3β/CREB signaling pathway
- From:
Chinese Journal of Pathophysiology
2024;40(11):1985-1992
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the impact of hippocampal protein phosphatase 1 regulator subunit 17(Ppp1r17)down-regulation on drinking-related behavior in mice,and to explore the protein kinase B(PKB/AKT)/glyco-gen synthase kinase-3β(GSK-3β)/cAMP response element binding protein(CREB)signaling pathway of Ppp1r17 in the development of alcohol dependence.METHODS:Forty male C57BL/6J mice were randomly divided into four groups(n=10):control group,shPpp1r17① group,shPpp1r17② group and shPpp1r17③ group.The mRNA and protein expression levels in the hippocampal tissues were evaluated after 3 weeks of AAV-shPpp1r17 injection.Twenty male C57BL/6J mice were randomly divided into a control group and a shPpp1r17 group(n=10).An open-field test,conditioned place prefer-ence(CPP)test and righting reflex test were performed.Furthermore,the localization and expression of AAV-shPpp1r17 were detected after 3 weeks of AAV-shPpp1r17 injection.Twenty male C57BL/6J mice were randomly divided into four groups(n=5):the empty virus+water group,the empty virus+EtOH group,the shPpp1r17+water group and the shPpp1r17+EtOH group.The EtOH group mice drank 9%alcohol continuously for 30 d.The protein expression levels of Ppp1r17,p-AKT,AKT,p-GSK-3β,GSK-3β,p-CREB and CREB were detected by Western blot.RESULTS:(1)The results of qPCR showed that Ppp1r17 was successfully suppressed by shPpp1r17.(2)The behavioral results showed that the shPpp1r17 group mice exhibited enhanced exercise ability and reduced anxiety-like emotions,and the downregulation of Ppp1r17 increased CPP scores and reduced the sensitivity of the mice to alcohol.(3)Immunofluorescence showed that AAV-shPpp1r17 was specifically expressed in the hippocampus.(4)Western blot analysis revealed that Ppp1r17 and the p-AKT/AKT,p-GSK-3β/GSK-3β and p-CREB/CREB ratios were significantly increased after treatment of EtOH.Howev-er,the protein expression of Ppp1r17 was significantly reduced,and the AKT/GSK-3β/CREB pathway was activated after knockdown of Ppp1r17 in the hippocampus.CONCLUSION:Ppp1r17 may suppress CREB phosphorylation through the AKT/GSK-3β/CREB pathway,thereby influencing alcohol drinking preference and locomotor behavior in mice.
