title: Reduction of α1GABAA receptor mediated by tyrosine kinase C (PKC) phosphorylation in a mouse model of fragile X syndrome.
abstract: Fragile X syndrome (FXS) caused by lack of fragile X mental retardation protein (Fmr1) is the most common cause of inherited intellectual disability and characterized by many cognitive disturbances like attention deficit, autistic behavior, and audiogenic seizure and have region-specific altered expression of some gamma-aminobutyric acid (GABAA) receptor subunits. Quantitative real-time polymerase chain reaction and western blot experiments were performed in the cultured cortical neurons and forebrain obtained from wild-type (WT) and Fmr1 KO mice demonstrate the reduction in the expression of α1 gamma-aminobutyric acid (α1GABAA) receptor, phospho-α1GABAA receptor, PKC and phosphor-PKC in Fmr1 KO mice comparing with WT mice, both in vivo and in vitro. Furthermore, we found that the phosphorylation of the α1GABAA receptor was mediated by PKC. Our results elucidate that the lower phosphorylation of the α1GABAA receptor mediated by PKC neutralizes the seizure-promoting effects in Fmr1 KO mice and point to the potential therapeutic targets of α1GABAA agonists for the treatment of fragile X syndrome.
authors.affiliation: Department of Habilitation, The Central Hospital of Xinxiang City Xinxiang, Henan Province, P. R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, The Third Affiliated Hospital of Xinxiang Medical College Henan Province, P. R. China.
authors.forename: Jiaqin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Habilitation, The Central Hospital of Xinxiang City Xinxiang, Henan Province, P. R. China.
authors.forename: Shunyi
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Habilitation, The Central Hospital of Xinxiang City Xinxiang, Henan Province, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Habilitation, The Central Hospital of Xinxiang City Xinxiang, Henan Province, P. R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yuan
keywords: Fragile X syndrome; tyrosine kinase C (PKC); α1GABAA receptor