Advances in Alzheimer’s Disease, 2017, 6, 13-31 http://www.scirp.org/journal/aad ISSN Online: 2169-2467 ISSN Print: 2169-2459 DOI: 10.4236/aad.2017.61002 March 10, 2017 Role of GSK3β and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease Teresa Ponce-Lopez 1,2* , Enrique Hong 1 , Manuel Abascal-Díaz 2 , Alfredo Meneses 1 1 Deparment of Pharmacobiology, CINVESTAV, México City, México 2 Faculty of Health Sciences, Anahuac University, Huixquilucan State of México, Mexico Abstract 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 patho- logical features of AD sporadic type (SAD). In this study, we investigated the role of glycogen synthase kinase 3β (GSK3β) 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 GSK3β (p-GSK3β) and PP2A in hippocampus and PFC, indicating that GSK3β 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 hy- perphosphorylation of tau and the cascade of insulin receptor signaling; con- firm that phosphatidyl-inositol-3 kinase-protein kinase B (PI3K-PKB/Akt- GSK3β) and PP2A are involved in the modulation of proteins responsible for the regulation of neurodegeneration in AD. Keywords Memory Deficit, Tau Hyperphosphorylation, GSK3β, PP2A, Streptozotocin, Hippocampus How to cite this paper: Ponce-Lopez, T., Hong, E., Abascal-Díaz, M. and Meneses, A. (2017) Role of GSK3β and PP2A on Re- gulation of Tau Phosphorylation in Hippo- campus and Memory Impairment in ICV- STZ Animal Model of Alzheimer’s Disease. Advances in Alzheimer’s Disease, 6, 13-31. https://doi.org/10.4236/aad.2017.61002 Received: January 21, 2017 Accepted: March 7, 2017 Published: March 10, 2017 Copyright © 2017 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access