DAPK1 regulates seizure-induced AD-like pathology
10.12360/CPB202405059
- VernacularTitle:DAPK1调控癫痫发作诱导的阿尔茨海默病样病变
- Author:
Yu-Lian ZOU
1
;
Zhou CHEN
;
Chen-Ling GAN
Author Information
1. 福建医科大学免疫治疗研究院
- Keywords:
epilepsy;
kainic acid;
death-associated protein kinase 1;
amyloid-β;
tau;
Alzheimer's disease
- From:
Chinese Pharmacological Bulletin
2024;40(12):2283-2288
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the regulation of death-associated protein kinase 1(DAPK1)on seizure-in-duced Alzheimer's disease(AD)-like pathology.Methods Two-month old C57BL/6 mice were given intraperitoneal injection of 25 mg·kg-1 kainic acid(KA)to establish a temporal lobe epilepsy(TLE)model,and control mice were injected with an equal a-mount of saline.The expression of key proteins in the amyloid metabolic pathway,the secretion of soluble am-yloid β-protein(Aβ),the high phosphorylation of tau,and the activation of DAPK1 pathway were detected in hippocampus of mice.WT mice and Dapk1 KO mice were given intraperitoneal injections of KA,then the effect of DAPK1 on seizure-induced AD-like pathology was examined.Results The secretion of soluble Aβ,the expression of key proteins in the amyloid metabolic pathway,the level of phosphorylation of tau,and the ex-pression and activity of DAPK1 were higher in the hip-pocampus of TLE mice than in the control mice.Com-pared with WT mice,KA-induced Aβ secretion and tau phosphorylation were significantly reduced in hippo-campus of Dapk1 KO mice.Conclusion TLE in-duces AD-like pathology in mice,and DAPK1 knockout alleviates symptoms of aging in mouse brain.
