GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease

PLoS One. 2012;7(8):e42823. doi: 10.1371/journal.pone.0042823. Epub 2012 Aug 13.

Abstract

Glial fibrillary acidic protein (GFAP) is the main astrocytic intermediate filament (IF). GFAP splice isoforms show differential expression patterns in the human brain. GFAPδ is preferentially expressed by neurogenic astrocytes in the subventricular zone (SVZ), whereas GFAP(+1) is found in a subset of astrocytes throughout the brain. In addition, the expression of these isoforms in human brain material of epilepsy, Alzheimer and glioma patients has been reported. Here, for the first time, we present a comprehensive study of GFAP isoform expression in both wild-type and Alzheimer Disease (AD) mouse models. In cortex, cerebellum, and striatum of wild-type mice, transcripts for Gfap-α, Gfap-β, Gfap-γ, Gfap-δ, Gfap-κ, and a newly identified isoform Gfap-ζ, were detected. Their relative expression levels were similar in all regions studied. GFAPα showed a widespread expression whilst GFAPδ distribution was prominent in the SVZ, rostral migratory stream (RMS), neurogenic astrocytes of the subgranular zone (SGZ), and subpial astrocytes. In contrast to the human SVZ, we could not establish an unambiguous GFAPδ localization in proliferating cells of the mouse SVZ. In APPswePS1dE9 and 3xTgAD mice, plaque-associated reactive astrocytes had increased transcript levels of all detectable GFAP isoforms and low levels of a new GFAP isoform, Gfap-ΔEx7. Reactive astrocytes in AD mice showed enhanced GFAPα and GFAPδ immunolabeling, less frequently increased vimentin and nestin, but no GFAPκ or GFAP(+1) staining. In conclusion, GFAPδ protein is present in SVZ, RMS, and neurogenic astrocytes of the SGZ, but also outside neurogenic niches. Furthermore, differential GFAP isoform expression is not linked with aging or reactive gliosis. This evidence points to the conclusion that differential regulation of GFAP isoforms is not involved in the reorganization of the IF network in reactive gliosis or in neurogenesis in the mouse brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Aging / pathology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Animals
  • Antibody Specificity
  • Astrocytes / metabolism*
  • Astrocytes / pathology*
  • Brain / metabolism*
  • Brain / pathology
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • Neurogenesis*
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • RNA, Messenger
  • glial fibrillary astrocytic protein, mouse

Grants and funding

This work was supported by the Internationale Stichting Alzheimer Onderzoek (ISAO; M.O. [#08504]) and the Netherlands Organization for Scientific Research (NWO; VICI grant to E.M.H. [865.09.003]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.