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Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein.
J Neurochem. 2007 May; 101(3):757-70.JN

Abstract

The intracerebroventricular (icv) application of streptozotocin (STZ) in low dosage was used in 3-month-old rats to explore brain insulin system dysfunction. Three months following STZ icv treatment, the expression of insulin-1 and -2 mRNA was significantly reduced to 11% in hippocampus and to 28% in frontoparietal cerebral cortex, respectively. Insulin receptor (IR) mRNA expression decreased significantly in frontoparietal cerebral cortex and hippocampus (16% and 33% of control). At the protein/activity level, different abnormalities of protein tyrosine kinase activity (increase in hippocampus), total IR beta-subunit (decrease in hypothalamus) and phosphorylated IR tyrosine residues (increase) became apparent. The STZ-induced disturbance in learning and memory capacities was not abolished by icv application of glucose transport inhibitors known to prevent STZ-induced diabetes mellitus. The discrepancy between reduced IR gene expression and increase in both phosphorylated IR tyrosine residues/protein tyrosine kinase activity may indicate imbalance between phosphorylation/dephosphorylation of the IR beta-subunit causing its dysfunction. These abnormalities may point to a complex brain insulin system dysfunction after STZ icv application, which may lead to an increase in hyperphosphorylated tau-protein concentration. Brain insulin system dysfunction is discussed as possible pathological core in the generation of hyperphosphorylated tau protein as a morphological marker of sporadic Alzheimer's disease.

Authors+Show Affiliations

Clinical Neurochemistry and National Parkinson Foundation Centre of Excellence Laboratory, Clinic for Psychiatry and Psychotherapy, Bayrische Julius-Maximilian University of Würzburg, Würzburg, Germany. edna.gruenblatt@mail.uni-wuerzburg.deNo 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

17448147

Citation

Grünblatt, Edna, et al. "Brain Insulin System Dysfunction in Streptozotocin Intracerebroventricularly Treated Rats Generates Hyperphosphorylated Tau Protein." Journal of Neurochemistry, vol. 101, no. 3, 2007, pp. 757-70.
Grünblatt E, Salkovic-Petrisic M, Osmanovic J, et al. Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J Neurochem. 2007;101(3):757-70.
Grünblatt, E., Salkovic-Petrisic, M., Osmanovic, J., Riederer, P., & Hoyer, S. (2007). Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. Journal of Neurochemistry, 101(3), 757-70.
Grünblatt E, et al. Brain Insulin System Dysfunction in Streptozotocin Intracerebroventricularly Treated Rats Generates Hyperphosphorylated Tau Protein. J Neurochem. 2007;101(3):757-70. PubMed PMID: 17448147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. AU - Grünblatt,Edna, AU - Salkovic-Petrisic,Melita, AU - Osmanovic,Jelena, AU - Riederer,Peter, AU - Hoyer,Siegfried, PY - 2007/4/24/pubmed PY - 2007/7/19/medline PY - 2007/4/24/entrez SP - 757 EP - 70 JF - Journal of neurochemistry JO - J Neurochem VL - 101 IS - 3 N2 - The intracerebroventricular (icv) application of streptozotocin (STZ) in low dosage was used in 3-month-old rats to explore brain insulin system dysfunction. Three months following STZ icv treatment, the expression of insulin-1 and -2 mRNA was significantly reduced to 11% in hippocampus and to 28% in frontoparietal cerebral cortex, respectively. Insulin receptor (IR) mRNA expression decreased significantly in frontoparietal cerebral cortex and hippocampus (16% and 33% of control). At the protein/activity level, different abnormalities of protein tyrosine kinase activity (increase in hippocampus), total IR beta-subunit (decrease in hypothalamus) and phosphorylated IR tyrosine residues (increase) became apparent. The STZ-induced disturbance in learning and memory capacities was not abolished by icv application of glucose transport inhibitors known to prevent STZ-induced diabetes mellitus. The discrepancy between reduced IR gene expression and increase in both phosphorylated IR tyrosine residues/protein tyrosine kinase activity may indicate imbalance between phosphorylation/dephosphorylation of the IR beta-subunit causing its dysfunction. These abnormalities may point to a complex brain insulin system dysfunction after STZ icv application, which may lead to an increase in hyperphosphorylated tau-protein concentration. Brain insulin system dysfunction is discussed as possible pathological core in the generation of hyperphosphorylated tau protein as a morphological marker of sporadic Alzheimer's disease. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/17448147/Brain_insulin_system_dysfunction_in_streptozotocin_intracerebroventricularly_treated_rats_generates_hyperphosphorylated_tau_protein_ L2 - https://doi.org/10.1111/j.1471-4159.2006.04368.x DB - PRIME DP - Unbound Medicine ER -