title: Phosphorylation of P42/P44 MAP kinase and DNA fragmentation in the rat perforant pathway stimulation model of limbic epilepsy.
abstract: The intracellular signaling pathways associated with neuronal injury after perforant pathway stimulation of the rodent hippocampus have not been examined. To determine whether activation of the p42/p44 (Erk1/2) MAP kinase (MAPK) phosphorylation cascade is linked to neuronal injury after perforant pathway stimulation (PPS), we stained for phosphorylated Erk1/2 (P-Erk1/2) and for DNA fragmentation, a marker of cell death after PPS. Eighteen Sprague-Dawley rats underwent PPS for 6 (n=6), 12 (n=6), or 24 (n=6) h and were sacrificed either immediately (n=9) or 48 h (n=9) after stimulation. Sham-operated non-stimulated control animals (n=2) and control animals receiving low frequency stimulation only (n=4) were also examined. Brain sections were stained for DNA fragmentation and P-Erk1/2. DNA fragmentation was evident only in granule cells and CA3 pyramidal cells of the stimulated side 48 h after 24 h of PPS. PPS resulted in robust phosphorylation of Erk1/2 that displayed a stereotyped timecourse, appearing first in hilar neurons on the ipsilateral side and later in hilar neurons, granule cells, hippocampal pyramidal and non-neuronal cell populations on both the stimulated and contralateral sides. Both Erk1/2 phosphorylation and DNA fragmentation show definite and reproducible staining patterns after PPS that vary based on duration of stimulation. Populations displaying Erk1/2 activation appeared to differ from those showing DNA fragmentation and neuronal injury.
authors.affiliation: Epilepsy Research Laboratory, Neurosurgical Service, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Brisman
authors.forename: G
authors.initials: G
authors.lastname: Rees Cosgrove
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cole
mesh_terms: D000818:Animals; D053938:DNA Fragmentation; D004558:Electric Stimulation; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology*; D008032:Limbic System / Q000503:physiopathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009420:Nervous System / Q000503:physiopathology; D019580:Perforant Pathway / Q000503:physiopathology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases