Naslov
Protein kinase B and glycogen synthase kinase-3 alterations in the brain in experimental Alzheimer's disease

Autori
Salkovic-Petrisic, Melita ; Tribl, Florian ; Schmidt, Manuela ; Hoyer, Siegfried ; Riederer, Peter

Izvornik
Journal of Neurochemistry

Vrsta, podvrsta
Ostale vrste radova, rukopis

Godina
2005

Ključne riječi
hippocampus; glycogen synthase kinase-3; protein kinase B; streptozotocin; Alzheimer's disease

Sažetak
The insulin resistance brain state is related to the late-onset sporadic Alzheimer’ s disease, and alterations of insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain. Confirmation studies have not been performed in an experimental model probably related to the sporadic Alzheimer’ s disease, e.g., rats showing a neuronal IR deficit subsequent to intracerebroventricular (icv) treatment with streptozotocin (STZ). In this study, Western blot analysis performed 1 month after STZ-icv treatment showed an increase (+63%) in the level of phosphorylated glycogen synthase kinase - 3α /β (pGSK-3α /β ) protein in the rat hippocampus, whereas the levels of GSK-3α /β and protein kinase B (Akt/PKB) remained unchanged. Three months after STZ-icv treatment, pGSK-3α /β and Akt/PKB levels tended to decrease (-8% and -9%, respectively). The changes were regionally specific, as a different pattern was found in frontal cortex. Structural alterations were also found, demonstrated as beta amyloid peptide like aggregates in brain capillaries of STZ-icv treated rats. Similar neurochemical changes and cognitive deficits were recorded in rats treated icv with 5-thio-D-glucose, a blocker of glucose transporter 2 (GLUT2) probably involved in brain glucose sensing. These results support the similarity of IR signalling cascade alteration and its consequences in STZ-icv treated rats, to those found in humans with sporadic Alzheimer’ s disease, and suggest a role of GLUT2 in its pathophysiology.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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