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Activation of p38MAPK in microglia after ischemia
K M Walton1, R DiRocco, B A Bartlett
1Department of Cell Biology, Cephalon, Inc., West Chester, Pennsylvania, USA.
Abstract:
p38MAPK has been implicated in the regulation of proinflammatory cytokines and apoptosis in vitro. To understand its role in neurodegeneration, we determined the time course and localization of the dually phosphorylated active form of p38MAPK in hippocampus after global forebrain ischemia. Phosphorylated p38MAPK and mitogen-activated protein kinase-activated protein 2 activity increased over 4 days after ischemia. Phosphorylated p38MAPK immunoreactivity was observed in microglia in regions adjacent to, but not in, the dying CA1 neurons. In contrast, neither c-Jun N-terminal kinase 1 nor p42/p44MAPK activity was altered after ischemia. These results provide the first evidence for localization of activated p38MAPK in the CNS and support a role for p38MAPK in the microglial response to stress.
Insights
Activated p38 mitogen-activated protein kinase (MAPK) is found in microglia following brain ischemia. This suggests p38MAPK plays a role in the brain
Area of Science:
- Neuroscience
- Cellular Biology
- Molecular Biology
Background:
- p38 mitogen-activated protein kinase (MAPK) regulates inflammatory cytokines and apoptosis in vitro.
- Its role in neurodegeneration remains unclear.
Purpose of the Study:
- To investigate the time course and localization of activated p38MAPK in the hippocampus after global forebrain ischemia.
- To elucidate the specific cell types involved in the p38MAPK response to ischemic stress.
Main Methods:
- Global forebrain ischemia was induced in a rodent model.
- Time course analysis of phosphorylated p38MAPK and mitogen-activated protein kinase-activated protein 2 activity.
- Immunohistochemical localization of phosphorylated p38MAPK in hippocampal tissue.
- Assessed activity of c-Jun N-terminal kinase 1 and p42/p44MAPK.
Main Results:
- Phosphorylated p38MAPK and MAPK-activated protein 2 activity increased over 4 days post-ischemia.
- Activated p38MAPK was localized in microglia adjacent to, but not within, dying CA1 neurons.
- No significant changes in c-Jun N-terminal kinase 1 or p42/p44MAPK activity were observed.
Conclusions:
- This study provides the first evidence of activated p38MAPK localization within the central nervous system (CNS) following ischemia.
- Results support a role for p38MAPK in the microglial response to ischemic stress in the brain.