Global cerebral ischemia that accompanies cardiac arrest is a major cause of morbidity and mortality. Protein Kinase C epsilon (PKCepsilon) is a member of the novel PKC subfamily and plays a vital role in ischemic preconditioning. Pharmacological activation of PKCepsilon before cerebral ischemia confers neuroprotection. The role of endogenous PKCepsilon after cerebral ischemia remains elusive. Here we used male PKCepsilon-null mice to assess the effects of PKCepsilon deficiency on neurodegeneration after transient global cerebral ischemia (tGCI). We found that the cerebral vasculature, blood flow, and the expression of other PKC isozymes were not altered in the PKCepsilon-null mice. Spatial learning and memory was impaired after tGCI, but the impairment was attenuated in male PKCepsilon-null mice as compared to male wild-type controls. A significant reduction in Fluoro-Jade C labeling and mitochondrial release of cytochrome C in the hippocampus was found in male PKCepsilon-null mice after tGCI. Male PKCepsilon-null mice expressed increased levels of PKCdelta in the mitochondria, which may prevent the translocation of PKCdelta from the cytosol to the mitochondria after tGCI. Our results demonstrate the neuroprotective effects of PKCepsilon deficiency on neurodegeneration after tGCI, and suggest that reduced mitochondrial translocation of PKCdelta may contribute to the neuroprotective action in male PKCepsilon-null mice.
Date:
2019-04
Relation:
Journal of Neuroscience Research. 2019 Apr;97(4):444-455.
