Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway

Šalković-Petrišić, Melita and Tribl, Florian and Schmidt, Manuela and Hoyer, Siegfried and Riederer, Peter (2006) Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. Journal of Neurochemistry, 96 (4). pp. 1005-1015. ISSN 0022-3042

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Abstract

The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain. These findings have not been confirmed in an experimental model related to sporadic Alzheimer's disease, for example rats showing a neuronal IR deficit subsequent to intracerebroventricular (i.c.v.) treatment with streptozotocin (STZ). In this study, western blot analysis performed 1 month after i.c.v. injection of STZ showed an increase of 63% in the level of phosphorylated glycogen synthase kinase-3α/β (pGSK-3α/β) protein in the rat hippocampus, whereas the levels of the unphosphorylated form (GSK-3α/β) and protein kinase B (Akt/PKB) remained unchanged. Three months after STZ treatment, pGSK-3α/β and Akt/PKB levels tended to decrease (by 8 and 9% respectively). The changes were region specific, as a different pattern was found in frontal cortex. Structural alterations were also found, characterized by β-amyloid peptide-like aggregates in brain capillaries of rats treated with STZ. Similar neurochemical changes and cognitive deficits were recorded in rats treated with i.c.v. 5-thio-d-glucose, a blocker of glucose transporter (GLUT)2, a transporter that is probably involved in brain glucose sensing. The IR signalling cascade alteration and its consequences in rats treated with STZ are similar to those found in humans with sporadic Alzheimer's disease, and our results suggest a role for GLUT2 in Alzheimer's pathophysiology.

Item Type: Article
MeSH: Alzheimer Disease - enzymology ; Diabetes Mellitus, Experimental - enzymology ; Frontal Lobe - enzymology ; Glycogen Synthase Kinase 3 - metabolism ; Hippocampus - enzymology ; Insulin - physiology ; Proto-Oncogene Proteins c-akt - metabolism ; Streptozocin - toxicity ; Animals ; Cognition ; Disease Models, Animal ; Injections, Intraventricular ; Male ; Maze Learning - drug effects ; Rats ; Rats, Wistar ; Signal Transduction ; Swimming
Departments: Katedra za farmakologiju
Depositing User: Lea Škorić
Status: Published
Creators:
CreatorsEmail
Šalković-Petrišić, MelitaUNSPECIFIED
Tribl, FlorianUNSPECIFIED
Schmidt, ManuelaUNSPECIFIED
Hoyer, SiegfriedUNSPECIFIED
Riederer, PeterUNSPECIFIED
Date: February 2006
Date Deposited: 12 Apr 2007
Last Modified: 23 Sep 2011 16:10
Subjects: /
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/259

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