Document Detail


A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities to and differences from the transgenic model (3xTg-AD mouse).
MedLine Citation:
PMID:  23150171     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alzheimer's disease (AD) can be divided into sporadic AD (SAD) and familial AD (FAD). Most AD cases are sporadic and result from multiple etiologic factors, including environmental, genetic, and metabolic factors, whereas FAD is caused by mutations in the presenilins or amyloid-β (Aβ) precursor protein (APP) genes. A commonly used animal model for AD is the 3xTg-AD transgenic mouse model, which harbors mutated presenilin 1, APP, and tau genes and thus represents a model of FAD. There is an unmet need in the field to characterize animal models representing different AD mechanisms, so that potential drugs for SAD can be evaluated preclinically in these animal models. A mouse model generated by intracerebroventricular (icv) administration of streptozocin (STZ), the icv-STZ mouse, shows many aspects of SAD. In this study, we compared the non-cognitive and cognitive behaviors as well as biochemical and immunohistochemical alterations between the icv-STZ mouse and the 3xTg-AD mouse. We found that both mouse models showed increased exploratory activity as well as impaired learning and spatial memory. Both models also demonstrated neuroinflammation, altered synaptic proteins and insulin/IGF-1 (insulin-like growth factor-1) signaling, and increased hyperphosphorylated tau in the brain. The most prominent brain abnormality in the icv-STZ mouse was neuroinflammation, and in the 3xTg-AD mouse it was elevation of hyperphosphorylated tau. These observations demonstrate the behavioral and neuropathological similarities and differences between the icv-STZ mouse and the 3xTg-AD mouse models and will help guide future studies using these two mouse models for the development of AD drugs.
Authors:
Yanxing Chen; Zhihou Liang; Julie Blanchard; Chun-Ling Dai; Shenggang Sun; Moon H Lee; Inge Grundke-Iqbal; Khalid Iqbal; Fei Liu; Cheng-Xin Gong
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Molecular neurobiology     Volume:  47     ISSN:  1559-1182     ISO Abbreviation:  Mol. Neurobiol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-06     Completed Date:  2014-02-13     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  8900963     Medline TA:  Mol Neurobiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  711-25     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / chemically induced*,  genetics,  pathology*
Animals
Cognition Disorders / chemically induced,  metabolism,  pathology
Disease Models, Animal*
Injections, Intraventricular
Maze Learning / drug effects,  physiology
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Transgenic
Streptozocin / administration & dosage,  toxicity*
Grant Support
ID/Acronym/Agency:
R01 AG027429/AG/NIA NIH HHS; R01 AG027429/AG/NIA NIH HHS; R03 TW008123/TW/FIC NIH HHS; R03 TW008123/TW/FIC NIH HHS
Chemical
Reg. No./Substance:
5W494URQ81/Streptozocin
Comments/Corrections

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