Masitinib attenuates neuropathological changes in acrolein-induced sAD model mice
JIA Kang
SHEN Qianhui
ZHANG Zhixian
LIU Yuan
PI Rongbiao
ZHOU Sigui
Abstract：Objective To explore the therapeutic effects of Masitinib in acrolein-induced sporadic Alzheimer's disease(sAD)model mice and explore its underlying mechanisms.Methods Male C57BL/6 mice were administered acrolein[3 mg·(kg·d)-1]by gavage for 10 weeks,with Masitinib[60 mg·(kg·d)-1]co-administered from the 5th week for 6 weeks.Behavioral tests,including the buried food pellet test,Morris water maze,Y-maze,open field test,and elevated plus maze,were conducted at the 9th week.Cortical and hippocampal tissues were then collected for pathological assessments using Western blotting,immunofluorescence staining,and Golgi-Cox staining.Results Masitinib significantly ameliorated acrolein-induced olfactory deficits,cognitive dysfunction,and anxiety-like behaviors.Furthermore,Masitinib not only reduced phosphorylated Tau(p-Tau)levels,increased postsynaptic density protein 95(PSD95)expression,and restored dendritic spine density but also exerted anti-neuroinflammatory effects by suppressing the NF-κB/NLRP3/caspase-1 sig-naling pathway and microglial activation.Conclusion This study is the first to demonstrate that Masitinib mitigates sAD progression through dual mechanisms involving cognitive improvement and neuroprotection,providing crucial experimental evidence for its clinical translation.
Keywords：MasitinibSporadic Alzheimer's diseaseAcroleinCognitive dysfunctionNeuroinflammation
Publication Date：2025-06-30
Online Publishing Date：2025-08-21(First online date of this platform, not the publication date of the document)
Pages：8( 528-535 )