title: Long-term valproate treatment increases brain neuropeptide Y expression and decreases seizure expression in a genetic rat model of absence epilepsy.
abstract: The mechanisms by which valproate, one of the most widely prescribed anti-epileptic drugs, suppresses seizures have not been fully elucidated but may involve up-regulation of neuropeptide Y (NPY). We investigated the effects of valproate treatment in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) on brain NPY mRNA expression and seizure control. GAERS were administered either valproate (42 mg.kg(-1) hr(-1)) or saline continuously for 5 days. Electroencephalograms were recorded for 24 hrs on treatment days 1, 3 and 5 and the percentage of time spent in seizure activity was analysed. NPY mRNA expression was measured in different brain regions using qPCR. Valproate treatment suppressed seizures by 80% in GAERS (p<0.05) and increased NPY mRNA expression in the thalamus (p<0.05) compared to saline treatment. These results demonstrate that long-term valproate treatment results in an upregulation of thalamic expression of NPY implicating this as a potential contributor to the mechanism by which valproate suppresses absence seizures.
authors.affiliation: Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia ; The Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Johanna
authors.initials: J
authors.lastname: Elms
authors.forename: Kim L
authors.initials: KL
authors.lastname: Powell
authors.forename: Leena
authors.initials: L
authors.lastname: van Raay
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dedeurwaerdere
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D009478:Neuropeptide Y; D014635:Valproic Acid
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