Cortical spreading depression transiently activates MAP kinases.
Cortical spreading depression (CSD) has been shown to have neuroprotective effects when administered in advance of cerebral ischemia. The mechanism by which CSD induces its neuroprotective effect however remains to be elucidated. Since MAP kinases have been shown to impart neuroprotection in ischemic preconditioning paradigms, we attempted to determine the role CSD may have in the activation of MAPK. We show that CSD is capable of increasing the phosphorylation of ERK in a MEK-dependent manner. This phosphorylation is, however, transient, as phosphorylated ERK levels return to control levels 45 min after 2 h of CSD elicitation. Immunohistochemical analysis reveals that the phosphorylated form of ERK is located ubiquitously in cells of the CSD-treated cortex while CSD-elicited MEK phosphorylation resides solely in the nuclei. These data suggest that CSD may act via the MAP kinase pathways to mediate preconditioning.
Chow
Ava K
AK
Neuroscience Research Institute, Faculty of Medicine, University of Ottawa, 451 Smyth, Ontario, Ottawa, Canada K1H 8M5.
Thompson
C S
CS
Hogan
Matthew J
MJ
Banner
D
D
Sabourin
L A
LA
Hakim
A M
AM
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology*; D002540:Cerebral Cortex / Q000201:enzymology* / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D019194:Ischemic Preconditioning; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology*
D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases