The effects of suberoylanilide hydroxamic acid on cognitive performance and cerebral tau phosphorylation in Alzheimer's disease transgenic mice / 中华神经科杂志

ABSTRACT

Objective To observe the effects of histone deacetylases inhibitor (HDACi) on cognitive performance and cerebral tau phosphorylation in transgenic mice coexpressed five familial Alzheimer' s disease mutations (5XFAD).Method The total 12 5XFAD-CC and 12 wild type (WT) mice were administrated with suberoylanilide hydroxamic acid ( SAHA,n =7) and vehicle ( n =5 ),respectively.The cognitive performance was assessed by Y-maze and Morris water maze.The protein levels of acetylated α-tubulin,total tau and phosphorylated tau and phosphorylated glycogen synthase kinase-3β (GSK3β) were determined by Western blotting.Results SAHA ameliorated learning and memory deficits in 5XFAD-CC mice (39.10％ ±2.25％,t =2.688,P =0.0312 for total numbers of entrance in novel arm; 26.81％ ±0.78％,t =3.271,P =0.017 for time spending in novel arm; F =5.936,P =0.045 for hidden platform;31.70％ ±4.21％,t =2.317,P =0.049 for probe trial).Administration of SAHA significantly increased acetylated α-tubulin in hippocampus of WT and 5XFAD-CC mice (26.42％ and 29.64％,respectively).Additionally,SAHA attenuated tau-pSer396,tau-pSer404 and tau-pThrThr231 in hippocampus of 5XFAD-CC mice (24.22％,48.98％ and 26.95％,respectively). Moreover,hippocampal phosphorylated GSK3β was markedly reduced in SAHA-treated 5XFAD-CC mice (31.29％). Conclusion SAHA may improve cognitive performance in 5XFAD-CC mice, which is associated with its significant effects on the phosphorylation of tau and GSK3β.