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Temporal correlation of the memory deficit with Alzheimer‐like lesions induced by activation of glycogen synthase kinase‐3
Author(s) -
Wang Yue,
Zhang JunXia,
Du XiaoXia,
Zhao Li,
Tian Qing,
Zhu LingQiang,
Wang ShaoHui,
Wang JianZhi
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05578.x
Subject(s) - hyperphosphorylation , hippocampus , gsk 3 , acetylcholine , chemistry , glycogen synthase , wortmannin , endocrinology , medicine , phosphorylation , biochemistry , phosphatidylinositol
We have reported that activation of glycogen synthase kinase‐3 (GSK‐3) by ventricle injection of wortmannin (WT) and GF‐109203X (GFX) induces Alzheimer‐like memory deficit in rats [Liu et al. , J. Neurochem. 87 (2003), 1333]. To further explore the factors responsible for the memory loss, we studied here the temporal alterations of GSK‐3, tau phosphorylation, β‐amyloid (Aβ), and acetylcholine (ACh) after injection of WT/GFX, and analyzed their correlation with the memory loss. We observed that the severe memory deficit occurred at 24 and 48 h, and simultaneously, GSK‐3 activation, tau hyperphosphorylation at Thr231, Ser396, and Ser404 and decline of ACh in hippocampus were detected, and these changes were mostly recovered at 72 and 96 h after the injection of WT/GFX. Remarkable increase of Aβ and intracellular accumulation of argentophilic substances were detected at 72 h. Pearson analysis showed that the memory deficit was correlated with GSK‐3 activation, tau hyperphosphorylation, and decline of ACh but not with Aβ overproduction. Our data provide direct evidence demonstrating that activation of GSK‐3 by WT/GFX may cause memory deficit through tau hyperphosphorylation and suppression of ACh in hippocampus.