Document Detail


Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice.
MedLine Citation:
PMID:  23038755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The accumulation of aggregated amyloid-β (Aβ) in amyloid plaques is a neuropathological hallmark of Alzheimer's disease (AD). Reactive astrocytes are intimately associated with amyloid plaques; however, their role in AD pathogenesis is unclear. We deleted the genes encoding two intermediate filament proteins required for astrocyte activation-glial fibrillary acid protein (Gfap) and vimentin (Vim)-in transgenic mice expressing mutant human amyloid precursor protein and presenilin-1 (APP/PS1). The gene deletions increased amyloid plaque load: APP/PS1 Gfap(-/-)Vim(-/-) mice had twice the plaque load of APP/PS1 Gfap(+/+)Vim(+/+) mice at 8 and 12 mo of age. APP expression and soluble and interstitial fluid Aβ levels were unchanged, suggesting that the deletions had no effect on APP processing or Aβ generation. Astrocyte morphology was markedly altered by the deletions: wild-type astrocytes had hypertrophied processes that surrounded and infiltrated plaques, whereas Gfap(-/-)Vim(-/-) astrocytes had little process hypertrophy and lacked contact with adjacent plaques. Moreover, Gfap and Vim gene deletion resulted in a marked increase in dystrophic neurites (2- to 3-fold higher than APP/PS1 Gfap(+/+)Vim(+/+) mice), even after normalization for amyloid load. These results suggest that astrocyte activation limits plaque growth and attenuates plaque-related dystrophic neurites. These activities may require intimate contact between astrocyte and plaque.
Authors:
Andrew W Kraft; Xiaoyan Hu; Hyejin Yoon; Ping Yan; Qingli Xiao; Yan Wang; So Chon Gil; Jennifer Brown; Ulrika Wilhelmsson; Jessica L Restivo; John R Cirrito; David M Holtzman; Jungsu Kim; Milos Pekny; Jin-Moo Lee
Related Documents :
23487765 - Arid4a and arid4b regulate male fertility, a functional link to the ar and rb pathways.
24434305 - Wheel-running mitigates psychomotor sensitization initiation but not post-sensitization...
23533175 - Lgr4-mediated wnt/β-catenin signaling in peritubular myoid cells is essential for sper...
23634895 - Knockout of 5-lipoxygenase prevents dexamethasone-induced tau pathology in 3xtg mice.
3917925 - The regulatory locus r lambda 1 affects the level of lambda 1 light chain synthesis in ...
23487765 - Arid4a and arid4b regulate male fertility, a functional link to the ar and rb pathways.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-04
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  27     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-03-07     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  187-98     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Protein Precursor / genetics*
Animals
Astrocytes / cytology*
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Mice
Presenilin-1 / genetics*
Real-Time Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
P01 NS32636/NS/NINDS NIH HHS; P30NS69329/NS/NINDS NIH HHS; R01 NS48283/NS/NINDS NIH HHS; R01 NS67905/NS/NINDS NIH HHS; R37 AG13956/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Presenilin-1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer's disease phenotypes in model mic...
Next Document:  PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment.