Electroshock seizures protect against apoptotic hippocampal cell death induced by adrenalectomy.
Seizures evoked by electroshock induce rapid changes in the expression of several genes in the adult brain, including those encoding for neurotrophic factors. Some of the neurotrophic factors induced by brief seizures such as basic fibroblast growth factor and nerve growth factor have been shown to have neuroprotective action. We reasoned therefore that these seizures may protect against neural injury. To test this hypothesis, we examined the effect of electroshock-induced seizures on the vulnerability to cell death in the hippocampus. Cell death was induced by adrenalectomy, which results in a highly selective apoptotic neuronal death in the dentate granule cell layer of the hippocampus. Daily electroshock seizures were administered for seven days to sham-operated and adrenalectomized rats. Neuronal degeneration was evaluated by the highly sensitive and reliable cupric-silver impregnation method. Animals experiencing electroshock seizures were completely protected against adrenalectomy-induced cell death, whereas adrenalectomized animals not exposed to electroshock seizures exhibited substantial neuronal cell degeneration in the dentate granule cell layer. Daily restraint stress did not prevent the adrenalectomy-induced neuronal death, indicating that the neuroprotective effect of the seizure treatment is not accounted for by stress. We conclude that brief controlled seizure-evoked neural activation may allow the sparing of otherwise vulnerable neuronal populations in the injured adult brain. This prompts a need to explore the possibility that controlled administration of electroshock seizures may have therapeutic potential in treating neurodegenerative disorders.
Masco
D
D
Department of Pharmacology, Georgetown University, Washington, DC 20007, USA.
Sahibzada
N
N
Switzer
R
R
Gale
K
K
D000315:Adrenalectomy; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001284:Atrophy; D018891:Dentate Gyrus / Q000473:pathology; D004597:Electroshock; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D013950:Thymus Gland / Q000473:pathology