NFATc2 Modulates Microglial Activation in the AβPP/PS1 Mouse Model of Alzheimer’s Disease
| Autor: | Colin K. Combs, Christopher M. Norris, Kendra L. Puig, Atreyi Ghatak, Susan D. Kraner, Gunjan D. Manocha |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mice Transgenic Plaque Amyloid Biology Microgliosis Article Cell Line Proinflammatory cytokine Amyloid beta-Protein Precursor 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Presenilin-1 medicine Animals Humans Gliosis RNA Messenger Cells Cultured Neuroinflammation NFATC Transcription Factors Microglia General Neuroscience Brain NFAT General Medicine medicine.disease Astrogliosis Cell biology Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Clinical Psychology 030104 developmental biology medicine.anatomical_structure Cytokines Geriatrics and Gerontology medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 58:775-787 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-151203 |
| Popis: | 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 isoform expression may exist between murine and human microglia, it appears that microglial NFAT activity is a viable target for modulating the proinflammatory changes that occur during AD. |
| Databáze: | OpenAIRE |
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