DA-JC1 improves circadian rhythm disorder induced by amyloid β-protein 31-35
10.3760/cma.j.issn.1006-7876.2018.05.008
- VernacularTitle:DA-JC1改善β-淀粉样蛋白31-35所致昼夜节律紊乱研究
- Author:
Rui ZHANG
1
;
Yuan YUAN
;
Jin ZHAO
;
Yanan REN
;
Changtu WANG
;
Li WANG
;
Xiaohui WANG
Author Information
1. 山西医科大学基础医学院病理教研室
- Keywords:
Circadian rhythm;
Amyloidogenic proteins;
Glucagon-like peptide-1;
Glucose-dependent insulinotropic polypeptide;
Biological clocks
- From:
Chinese Journal of Neurology
2018;51(5):369-375
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of DA-JC1 on the circadian rhythm disorder in C57BL/6 mice and the abnormal expression of period1 in HT22 cells induced by amyloid β-protein 31-35 (Aβ31-35).Methods (1) The six-eight weeks old C57BL/6 male mice were selected for wheelrunning behavior experiment.Then we analyzed the effect of DA-JC1 on the circadian rhythm disorder induced by Aβ31-35.(2) HT22 mouse hippocampal cells were adopted as the research objects.Cells were divided into vehicle group,Aβ31-35 group,pre-DA-JC1 group and DA-JC1 group (n =4 respectively) by random number table method.Cell viability was assessed by methylthiazolyldiphenyl-tetrazolium bromide cytotoxicity assay.Real-time quantitative PCR was used to detect the expression of clock gene period1,and Western blotting was applied to examine the expression of period1 protein at circadian time (CT) 12.Results (1) Compared with the vehicle group ((23.54 ± 0.07) h),the circadian rhythm of mice in the Aβ31-35 group was disturbed which exhibited significantly longer free running period ((23.80 ± 0.06) h,t=0.265,P=0.010),whereas the disruption was significantly relieved with pre-treatment of DA-JC1 ((23.61 ± 0.06) h,t =0.193,P =0.047).(2) Compared with the vehicle group (100.0％ ± 3.6％),5 μmol/L Aβ31-35 decreased the cell viability significantly (78.7％ ± 3.4％,t =12.393,P =0.005),and DA-JC1 can reduce the toxicity of Aβ31-35 in HT22 cells (89.2％ ± 2.3％,t =9.748,P =0.048).(3) Compared with the vehicle group (period1 gene:1.00 ± 0.09;period1 protein:1.01 ± 0.07),abnormal rhythmic expression of period1 was induced by Aβ31-35 in HT22 cells which significantly decreased at CT12 (period1 gene:0.58 ± 0.04,t =0.419,P =0.001;period1 protein:0.74 ± 0.07,t =0.221,P =0.007) while DA-JC1 pre-treatment can reverse the abnormal expression (period1 gene:0.79 ±0.11,t =0.279,P=0.024;period1 protein:0.99 ±0.05,t=0.226,P=0.009).Conclusion DA-JC1 improves the circadian rhythm disorder induced by Aβ31-35 in C57BL/6 mice and improves the abnormal expression of period1 induced by Aβ31-35 in HT22 cells.
