Electroconvulsive shock exposure prevents neuronal apoptosis after kainic acid-evoked status epilepticus.
In the aftermath of prolonged continuous seizure activity (status epilepticus, SE), neuronal cell death occurs in the brain regions through which the seizure propagates. The vulnerability to adrenalectomy-induced apoptotic neuronal death was recently reported to be reduced by prior exposure to repeated daily noninjurious electroconvulsive shock (ECS). The present studies identified apoptosis and apoptosis-associated gene products in the neurodegenerative response to experimentally controlled periods (1 or 2 h) of SE in the rat, and determined whether exposure to ECS can interrupt these apoptotic responses mechanisms. Internucleosomal DNA fragmentation and the presence of apoptotic-like neurons (as assessed by in situ double labeling technique) was detected in hippocampus and rhinal cortex at 24 h after SE. Under these conditions, levels of both mRNA and protein encoded by the 'death promoting' bcl-XS gene were increased in the same brain areas. Pretreatment of animals for 7 days with low intensity (minimal) ECS conferred resistance to SE-evoked neurodegeneration, as assessed histopathologically by silver staining. Associated with this neuroprotective action was a reduction in the incidence of apoptosis-like neuronal morphology and DNA fragmentation, and a prevention of the increase in Bcl-XS protein and mRNA in hippocampus and rhinal cortex. These data suggest that pre-exposure to controlled, brief noninjurious seizures decreases vulnerability to programmed neuronal cell death, that this neuroprotective action occurs upstream from Bcl-XS, and that increases in bcl-XS gene expression may serve as a sensitive indicator of neurodegeneration following SE.
Kondratyev
A
A
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA. kondrata@georgetown.edu
Sahibzada
N
N
Gale
K
K
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D053938:DNA Fragmentation; D004565:Electroconvulsive Therapy; D018728:Entorhinal Cortex / Q000473:pathology / Q000502:physiology; D018690:Excitatory Amino Acid Agonists; D015870:Gene Expression; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D007608:Kainic Acid; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D015415:Biomarkers; D018690:Excitatory Amino Acid Agonists; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D007608:Kainic Acid