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Published on: May 3, 2017
p38 activation occurs mainly in microglia in the P301S Tauopathy mouse model
Juan R Perea1,2, Esther García1, Laura Vallés-Saiz1
1Centro de Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid (UAM-CSIC) (Campus de Cantoblanco), 1 Nicolás Cabrera st, 28049, Madrid, Spain.
Abstract:
Tauopathies are a group of neurodegenerative diseases characterized by the accumulation of hyperphosphorylated tau protein in the brain. Many of these pathologies also present an inflammatory component determined by the activation of microglia, the resident immune cells of the brain. p38 MAPK is one of the molecular pathways involved in neuroinflammation. Although this kinase is expressed mainly in glia, its activation in certain neurodegenerative diseases such as Alzheimer's Disease has been associated with its ability to phosphorylate tau in neurons. Using the P301S Tauopathy mouse model, here we show that p38 activation increases during aging and that this occurs mainly in microglia of the hippocampus rather than in neurons. Furthermore, we have observed that these mice present an activated microglial variant called rod microglia. Interestingly, p38 activation in this subpopulation of microglia is decreased. On the basis of our findings, we propose that rod microglia might have a neuroprotective phenotype in the context of tau pathology.
Insights
In tauopathies, p38 MAPK activation increases with age, primarily in microglia. Rod microglia, an activated form, show decreased p38 activation, suggesting a neuroprotective role in tau pathology.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Tauopathies involve hyperphosphorylated tau accumulation and neuroinflammation via microglia activation.
- p38 MAPK pathway is implicated in neuroinflammation and tau phosphorylation, with expression in glia and neurons.
Purpose of the Study:
- To investigate the role and localization of p38 MAPK activation in a P301S tauopathy mouse model.
- To explore the phenotype of microglia, specifically rod microglia, in the context of aging and tau pathology.
Main Methods:
- Utilized the P301S Tauopathy mouse model.
- Analyzed p38 MAPK activation levels in microglia and neurons during aging.
- Characterized microglial morphology, identifying rod microglia.
Main Results:
- p38 MAPK activation increased with aging in the hippocampus, predominantly in microglia, not neurons.
- Rod microglia, an activated microglial subtype, were observed in the model.
- p38 MAPK activation was found to be decreased in this rod microglia subpopulation.
Conclusions:
- Aging exacerbates p38 MAPK activation in hippocampal microglia in this tauopathy model.
- Rod microglia may represent a neuroprotective phenotype, as they exhibit reduced p38 MAPK activation despite the overall increase in neuroinflammation.
