%0 Journal Article
%T Role of GSK3<i>¦Â</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer¡¯s Disease
%A Teresa Ponce-Lopez
%A Enrique Hong
%A Manuel Abascal-D¨ªaz
%A Alfredo Meneses
%J Advances in Alzheimer's Disease
%P 13-31
%@ 2169-2467
%D 2017
%I Scientific Research Publishing
%R 10.4236/aad.2017.61002
%X Intracerebroventricular administration (ICV) of streptozotocin (STZ) in rats has been associated to desensitization of the insulin receptor (IR) and biochemical changes similar to those occurring in Alzheimer¡¯s disease (AD) or older brains, so it has been proposed as a suitable model for studying some of the pathological features of AD sporadic type (SAD). In this study, we investigated the role of glycogen synthase kinase 3<i>¦Â</i> (GSK3<i>¦Â</i>) and protein phosphatase 2A (PP2A) in the regulation of the phosphorylation of tau (p-tau). Results showed that ICV-STZ treated rats had deficits in short- (1.5-h) and long-term (24- and 48-h) memory after one month of ICV-STZ treatment and six months relative to control rats. The memory deficit was associated to increasing [F(3, 12) = 31.48, p < 0.0001] p-tau in the hippocampus but not in prefrontal cortex (PFC). Likewise, STZ reduced phosphorylation of GSK3<i>¦Â</i> (p-GSK3<i>¦Â</i>) and PP2A in hippocampus and PFC, indicating that GSK3<i>¦Â</i> and PP2A contributed to regulation of p-tau. These data supporting the model with ICV-STZ in rat are adequate to study the progressive memory impairment associated to hyperphosphorylation of tau and the cascade of insulin receptor signaling; confirm that phosphatidyl-inositol-3 kinase-protein kinase B (PI3K-PKB/Akt-GSK3<i>¦Â</i>) and PP2A are involved in the modulation of proteins responsible for the regulation of neurodegeneration in AD.
%K Memory Deficit
%K Tau Hyperphosphorylation
%K GSK3&lt
%K i&gt
%K ¦Â&lt
%K /i&gt
%K PP2A
%K Streptozotocin
%K Hippocampus
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=74645