title: Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein.
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: 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.de
authors: Edna
authors: E
authors: Grünblatt
authors: Melita
authors: M
authors: Salkovic-Petrisic
authors: Jelena
authors: J
authors: Osmanovic
authors: Peter
authors: P
authors: Riederer
authors: Siegfried
authors: S
authors: Hoyer
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D013311:Streptozocin; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D016875:tau Proteins; D013311:Streptozocin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin