Tags

Type your tag names separated by a space and hit enter

Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease.
J Neural Transm (Vienna). 2015 Apr; 122(4):577-92.JN

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10000, Zagreb, Croatia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25808906

Citation

Knezovic, Ana, et al. "Staging of Cognitive Deficits and Neuropathological and Ultrastructural Changes in Streptozotocin-induced Rat Model of Alzheimer's Disease." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 122, no. 4, 2015, pp. 577-92.
Knezovic A, Osmanovic-Barilar J, Curlin M, et al. Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease. J Neural Transm (Vienna). 2015;122(4):577-92.
Knezovic, A., Osmanovic-Barilar, J., Curlin, M., Hof, P. R., Simic, G., Riederer, P., & Salkovic-Petrisic, M. (2015). Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease. Journal of Neural Transmission (Vienna, Austria : 1996), 122(4), 577-92. https://doi.org/10.1007/s00702-015-1394-4
Knezovic A, et al. Staging of Cognitive Deficits and Neuropathological and Ultrastructural Changes in Streptozotocin-induced Rat Model of Alzheimer's Disease. J Neural Transm (Vienna). 2015;122(4):577-92. PubMed PMID: 25808906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease. AU - Knezovic,Ana, AU - Osmanovic-Barilar,Jelena, AU - Curlin,Marija, AU - Hof,Patrick R, AU - Simic,Goran, AU - Riederer,Peter, AU - Salkovic-Petrisic,Melita, Y1 - 2015/03/26/ PY - 2015/03/03/received PY - 2015/03/09/accepted PY - 2015/3/27/entrez PY - 2015/3/27/pubmed PY - 2015/12/19/medline SP - 577 EP - 92 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 122 IS - 4 N2 - 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. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/25808906/Staging_of_cognitive_deficits_and_neuropathological_and_ultrastructural_changes_in_streptozotocin_induced_rat_model_of_Alzheimer's_disease_ L2 - https://doi.org/10.1007/s00702-015-1394-4 DB - PRIME DP - Unbound Medicine ER -