title: Down-regulated expression of acid-sensing ion channel 1a in cortical lesions of patients with focal cortical dysplasia.
abstract: Focal cortical dysplasia (FCD) represents a well-recognized cause of medically intractable epilepsy. Previous studies have indicated that seizures can reduce brain pH and then eliminate seizure discharges. Acid-sensing ion channels (ASICs) are H(+)-gated cation channels that are widely expressed in the central and peripheral nervous systems. To understand the potential roles of ASIC1a in the epileptogenesis of FCD, we investigated the expression and distribution patterns of ASIC1a in surgical specimens from patients with FCD and age-matched normal cortices (CTX). Decreased ASIC1a messenger RNA (mRNA) and protein expression were detected in FCD compared with CTX. Moreover, the expression of ASIC1a was significantly lower in FCD type II than FCD type I. Immunohistochemistry results indicated that the overall immunoreactivity of the ASIC1a staining was diminished in the dysplastic cortices of FCD compared to the CTX samples. In FCD, ASIC1a immunoreactivity was mainly observed in reactive astrocytes and a minority of malformed cells, including hypertrophic neurons, dysmorphic neurons, and balloon cells. Confocal analysis demonstrated that most malformed cells expressing ASIC1a were co-labeled with neuronal rather than astrocytic markers, indicating a neuronal lineage. In conclusion, the downregulation and altered cellular distribution of ASIC1a in FCD suggest that ASIC1a may potentially contribute to the epileptogenesis of FCD.
authors.affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, 2-V Xinqiao Street, 400037, Chongqing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Jiao-Jiang
authors.initials: JJ
authors.lastname: He
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Wei
authors.forename: Zheng-Le
authors.initials: ZL
authors.lastname: Zang
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Chun-Qing
authors.initials: CQ
authors.lastname: Zhang
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D004827:Epilepsy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D065703:Malformations of Cortical Development, Group I / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D012333:RNA, Messenger