title: Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy.
abstract: Due to the involvement of cortical neurons in spike-wave discharge (SWD) initiation, and the contribution of voltage-gated sodium channels (VGSCs) to neuronal firing, we examined alterations in the expression of VGSC mRNA and protein in cortical neurons in the WAG/Rij absence epileptic rat. WAG/Rij rats were compared to age-matched Wistar control rats at 2, 4, and 6 months. Continuous EEG data was recorded, and percent time in SWD was determined. Tissue from different cortical locations from WAG/Rij and Wistar rats was analyzed for VGSC mRNA (by quantitative PCR) and protein (by immunocytochemistry). SWDs increased with age in WAG/Rij rats. mRNA levels for sodium channels Nav1.1 and Nav1.6, but not Nav1.2, were found to be up-regulated selectively within the facial somatosensory cortex (at AP +0.0, ML +6.0 mm). Protein levels for Nav1.1 and Nav1.6 were up-regulated in layer II-IV cortical neurons in this region of cortex. No significant changes were seen in adjacent regions or other brain areas, including the pre-frontal and occipital cortex. In the WAG/Rij model of absence epilepsy, we identified a specific region of cortex, in layer II-IV neurons on the lateral convexity of the cortex in the facial somatosensory area, where mRNA and protein expression of sodium channel genes Nav1.1 and Nav1.6 are up-regulated. This region of cortex approximately matches the electrophysiologically determined region of seizure onset. Changes in the expression of Nav1.1 and Nav1.6 parallel age-dependent increases in seizure frequency and duration.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, and Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Klein
authors.forename: Davender S
authors.initials: DS
authors.lastname: Khera
authors.forename: Hrachya
authors.initials: H
authors.lastname: Nersesyan
authors.forename: Eyal Y
authors.initials: EY
authors.lastname: Kimchi
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.forename: Hal
authors.initials: H
authors.lastname: Blumenfeld
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels