NFATc2 Modulates Microglial Activation in the AβPP/PS1 Mouse Model of Alzheimer's Disease.

Journal of Alzheimer's Disease : JAD
Gunjan D ManochaColin Kelly Combs

Abstract

Alzheimer's disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide. We observed that the NFATc2 isoform was the most highly expressed in murine microglia cultures, and inhibition or deletion of NFATc2 was sufficient to attenuate the ability of the microglia to secrete cytokines. In order to determine whether the NFATc2 isoform, in particular, was a valid immunomodulatory target in vivo, we crossed an NFATc2-/- line to a well-known AD mouse model, an AβPP/PS1 mouse line. As expected, the AβPP/PS1 x NFATc2-/- mice had attenuated cytokine levels compared to AβPP/PS1 mice as well as reduced microgliosis and astrogliosis with no effect on plaque load. Although some species differences in relative ...Continue Reading

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Citations

Feb 7, 2019·Journal of Leukocyte Biology·Shoutang Wang, Marco Colonna
Jul 25, 2018·Frontiers in Aging Neuroscience·Pradoldej Sompol, Christopher M Norris
Oct 10, 2018·Frontiers in Aging Neuroscience·Susan D Kraner, Christopher M Norris
Aug 4, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Meredith J GiblinJohn S Penn

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Methods Mentioned

BETA
transgenic
transfection
ELISA
ELISAs
PCR
dissection

Software Mentioned

Adobe Photoshop

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