Viral risk factor for seizures: pathobiology of dynorphin in herpes simplex viral (HSV-1) seizures in an animal model.
Up to 89% of patients with herpes simplex virus type-1 (HSV-1) encephalitis can have seizures. Possibly, viruses are environmental triggers for seizures in genetically vulnerable individuals. Inherited dynorphin promoter polymorphisms are associated with temporal lobe epilepsy and febrile seizures in man. In animals, the dynorphin system in the hippocampus regulates excitability. The hypothesis that reduced dynorphin expression in dentate gyrus of hippocampus due to HSV-1 infection leads to epileptic responses was tested in a rat model of HSV-1 encephalitis using EEG recording, histopathological and neuropharmacologic probes. HSV-1 infection causes loss of dynorphin A-like immunoreactivity in hippocampus, an effect independent of direct viral interference and cell loss. A kappa opioid receptor agonist U50488 effectively blocks ictal activity, linking absence of dynorphin to propensity for epileptic activity. These findings show a vulnerability of hippocampal dynorphin during infection, suggesting a neurochemical basis for seizures that may be generalizable to other encephalitic viruses.
Solbrig
Marylou V
MV
Department of Neurology, University of California-Irvine, Irvine, CA 92697-4292, USA. msolbrig@uci.edu
Adrian
Russell
R
Chang
Daniel Y
DY
Perng
Guey-Chuen
GC
D000200:Action Potentials / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004399:Dynorphins / Q000172:deficiency* / Q000235:genetics; D004569:Electroencephalography; D020803:Encephalitis, Herpes Simplex / Q000150:complications*; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism; D012307:Risk Factors
D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa; D004399:Dynorphins