GFAP and Vimentin Deficiency Alters Gene Expression in Astrocytes and Microglia in Wild-Type Mice and Changes the Transcriptional Response of Reactive Glia in Mouse Model for Alzheimer's Disease

W Kamphuis, L Kooijman, M Orre, Oscar Stassen, M Pekny, EM Hol

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

80 Citeringar (Scopus)

Sammanfattning

Reactive astrocytes with an increased expression of intermediate filament (IF) proteins Glial Fibrillary Acidic Protein (GFAP) and Vimentin (VIM) surround amyloid plaques in Alzheimer's disease (AD). The functional consequences of this upregulation are unclear. To identify molecular pathways coupled to IF regulation in reactive astrocytes, and to study the interaction with microglia, we examined WT and APPswe/PS1dE9 (AD) mice lacking either GFAP, or both VIM and GFAP, and determined the transcriptome of cortical astrocytes and microglia from 15- to 18-month-old mice. Genes involved in lysosomal degradation (including several cathepsins) and in inflammatory response (including Cxcl5, Tlr6, Tnf, Il1b) exhibited a higher AD-induced increase when GFAP, or VIM and GFAP, were absent. The expression of Aqp4 and Gja1 displayed the same pattern. The downregulation of neuronal support genes in astrocytes from AD mice was absent in GFAP/VIM null mice. In contrast, the absence of IFs did not affect the transcriptional alterations induced by AD in microglia, nor was the cortical plaque load altered. Visualizing astrocyte morphology in GFAP-eGFP mice showed no clear structural differences in GFAP/VIM null mice, but did show diminished interaction of astrocyte processes with plaques. Microglial proliferation increased similarly in all AD groups. In conclusion, absence of GFAP, or both GFAP and VIM, alters AD-induced changes in gene expression profile of astrocytes, showing a compensation of the decrease of neuronal support genes and a trend for a slightly higher inflammatory expression profile. However, this has no consequences for the development of plaque load, microglial proliferation, or microglial activation. GLIA 2015;63:1036-1056
OriginalspråkOdefinierat/okänt
Sidor (från-till)1036–1056
Antal sidor21
TidskriftGlia
Volym63
Utgåva6
DOI
StatusPublicerad - 2015
MoE-publikationstypA1 Tidskriftsartikel-refererad

Nyckelord

  • GFAP
  • A
  • gliosis
  • microglia
  • Vimentin
  • astrocytes

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