Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach

Scientific paper - Original scientific paper

• Author: Melita Šalković-Petrišić
• Author: Siegfried Hoyer
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

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.

• Keywords (english): 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
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Journal of Neural Transmission. Supplementum
• Numbering: vol. 72, pp. 217-33
• p-ISSN: 0303-6975
• DOI: https://doi.org/10.1007/978-3-211-73574-9_28
• URN:NBN: urn:nbn:hr:105:989050
• Publication: 2007-12-28
• Document URL: https://doi.org/10.1007/978-3-211-73574-9_28
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 11:35:23