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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.
J Neurochem. 2006 Feb; 96(4):1005-15.JN

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-3alpha/beta (pGSK-3alpha/beta) protein in the rat hippocampus, whereas the levels of the unphosphorylated form (GSK-3alpha/beta) and protein kinase B (Akt/PKB) remained unchanged. Three months after STZ treatment, pGSK-3alpha/beta 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 beta-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.

Authors+Show Affiliations

Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia. melitas@mef.hrNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16412093

Citation

Salkovic-Petrisic, Melita, et al. "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, vol. 96, no. 4, 2006, pp. 1005-15.
Salkovic-Petrisic M, Tribl F, Schmidt M, et al. 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. J Neurochem. 2006;96(4):1005-15.
Salkovic-Petrisic, M., Tribl, F., Schmidt, M., Hoyer, S., & Riederer, P. (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), 1005-15.
Salkovic-Petrisic M, et al. 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. J Neurochem. 2006;96(4):1005-15. PubMed PMID: 16412093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Salkovic-Petrisic,Melita, AU - Tribl,Florian, AU - Schmidt,Manuela, AU - Hoyer,Siegfried, AU - Riederer,Peter, Y1 - 2006/01/12/ PY - 2006/1/18/pubmed PY - 2006/4/7/medline PY - 2006/1/18/entrez SP - 1005 EP - 15 JF - Journal of neurochemistry JO - J Neurochem VL - 96 IS - 4 N2 - 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-3alpha/beta (pGSK-3alpha/beta) protein in the rat hippocampus, whereas the levels of the unphosphorylated form (GSK-3alpha/beta) and protein kinase B (Akt/PKB) remained unchanged. Three months after STZ treatment, pGSK-3alpha/beta 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 beta-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. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16412093/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_ L2 - https://doi.org/10.1111/j.1471-4159.2005.03637.x DB - PRIME DP - Unbound Medicine ER -