p38 activation occurs mainly in microglia in the P301S Tauopathy mouse model

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.

Automated summary

Tauopathies are neurodegenerative diseases characterized by the accumulation of hyperphosphorylated tau protein. Inflammation, particularly the activation of microglia, is also involved in these diseases. The p38 MAPK pathway, primarily expressed in glia, has been associated with tau phosphorylation in neurodegenerative diseases like Alzheimer's Disease. Using a mouse model, researchers found increased p38 activation in microglia of the hippocampus during aging. Interestingly, these mice also displayed activated rod microglia, although p38 activation was decreased in this subpopulation. This suggests that rod microglia may have a neuroprotective phenotype in the context of tau pathology.