Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease

Scientific paper - Original scientific paper

• Author: Ana Knezović
• Author: Jelena Osmanović-Barilar
• Author: Marija Ćurlin
• Author: Patrick R. Hof
• Author: Goran Šimić
• Author: Peter Riederer
• Author: Melita Šalković-Petrišić
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

Sporadic Alzheimer's disease (sAD) is the most common form of dementia. Rats injected intracerebroventricularly with streptozotocin (STZ-icv) develop insulin-resistant brain state and represent a non-transgenic sAD model with a number of AD-like cognitive and neurochemical features. We explored cognitive, structural and ultrastructural changes in the brain of the STZ-icv rat model over a course of 9 months. Cognitive functions were measured in the STZ-icv- (0.3, 1 and 3 mg/kg) and age-matched control rats by passive avoidance test. Structural changes were assessed by Nissl and Bielschowsky silver staining. Immunohistochemistry and electron microscopy analysis were used to detect amyloid β- (Aβ(1-42)) and hyperphosphorylated tau (AT8) accumulation and ultrastructural changes in the brain. Memory decline was time- (≤3 months/acute, ≥3 months/progressive) and STZ-icv dose-dependent. Morphological changes were manifested as thinning of parietal cortex (≥1 month) and corpus callosum (9 months), and were more pronounced in the 3 mg/kg STZ group. Early neurofibrillary changes (AT8) were detected from 1 month onward in the neocortex, and progressed after 3 months to the hippocampus. Intracellular Aβ(1-42) accumulation was found in the neocortex at 3 months following STZ-icv treatment, while diffuse Aβ(1-42)-positive plaque-like formations were found after 6 months in the neocortex and hippocampus. Ultrastructural changes revealed enlargement of Golgi apparatus, pyknotic nuclei, and time-dependent increase in lysosome size, number, and density. Our data provide a staging of cognitive, structural/ultrastructural, and neuropathological markers in the STZ-icv rat model that in many aspects seems to be generally comparable to stages seen in human sAD.

• Keywords (english): Alzheimer Disease/complications; Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Alzheimer Disease/psychology; Amyloid beta-Peptides/metabolism; Animals; Avoidance Learning; Brain/metabolism; Brain/pathology; Cognition Disorders/etiology; Cognition Disorders/metabolism; Cognition Disorders/pathology; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Immunohistochemistry; Intermediate Filaments/metabolism; Intracellular Space/metabolism; Male; Microscopy, Electron; Neurons/metabolism; Neurons/pathology; Peptide Fragments/metabolism; Phosphorylation; Plaque, Amyloid/metabolism; Plaque, Amyloid/pathology; Rats, Wistar; Streptozocin; 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
• Numbering: vol. 122, no. 4, pp. 577-592
• p-ISSN: 0300-9564
• DOI: https://doi.org/10.1007/s00702-015-1394-4
• URN:NBN: urn:nbn:hr:105:301217
• Publication: 2015-04
• Document URL: https://doi.org/10.1007/s00702-015-1394-4
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 08:37:30