Šalković-Petrišić, Melita and Hoyer, Siegfried
Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach.
Journal of Neural Transmission. Supplementum, 72.
A growing body of evidence implicates impairments in brain insulin signaling in early sporadic Alzheimer disease (sAD) pathology. However, the most widely accepted hypothesis for AD aetiology stipulates that pathological aggregations of the amyloid beta (Abeta) peptide are the cause of all forms of Alzheimer's disease. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats are proposed as a probable experimental model of sAD. The current work reviews evidence obtained from this model indicating that central STZ administration induces brain pathology and behavioural alterations resembling those in sAD patients. Recently, alterations of the brain insulin system resembling those in sAD have been found in the STZ-icv rat model and are associated with tau protein hyperphosphorylation and Abeta-like aggregations in meningeal vessels. In line with these findings the hypothesis has been proposed that insulin resistance in the brain might be the primary event which precedes the Abeta pathology in sAD.
||Alzheimer Disease/chemically induced ; Alzheimer Disease/pathology ; Alzheimer Disease/physiopathology ; Amyloid beta-Protein/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Blood Glucose/metabolism ; Brain/drug effects ; Brain/pathology ; Brain/physiopathology ; Disease Models, Animal ; Glucose Transporter Type 4/drug effects ; Glucose Transporter Type 4/physiology ; Humans ; Injections, Intraventricular ; Insulin/physiology ; Insulin Resistance/physiology ; Learning/drug effects ; Learning/physiology ; Memory/drug effects ; Memory/physiology ; Neurotoxins/pharmacology ; Rats ; Receptor, Insulin/drug effects ; Receptor, Insulin/physiology ; Receptors, Cell Surface/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Streptozocin/pharmacology ; tau Proteins/metabolism
||Katedra za farmakologiju
||28 December 2007
||15 Mar 2010
||23 Sep 2011 16:11
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