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

Knezović, Ana and Osmanović-Barilar, Jelena and Ćurlin, Marija and Hof, Patrick R. and Šimić, Goran and Riederer, Peter and Šalković-Petrišić, Melita (2015) Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease. Journal of Neural Transmission, 122 (4). pp. 577-592. ISSN 0300-9564

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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.

Item Type: Article
MeSH: 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
Departments: Katedra za farmakologiju
Depositing User: Marijan Šember
Status: Published
Osmanović-Barilar, JelenaUNSPECIFIED
Riederer, PeterUNSPECIFIED
Šalković-Petrišić, MelitaUNSPECIFIED
Date: April 2015
Date Deposited: 06 Apr 2016 09:24
Last Modified: 23 Jul 2020 07:13
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