title: Regulation of alternative splicing of NMDAR1 in the kindling model.
abstract: Kindling refers to a phenomenon in which repeated application of initially subconvulsive electrical stimulations produces limbic and clonic motor seizures of progressively increasing severity. Once established, the increased excitability is lifelong. Several lines of investigation suggest that the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor participates in the expression of the increased neuronal excitability of the kindled brain. Many studies demonstrate that kindling results in altered NMDA receptor functional and pharmacological properties, indicating that kindling may cause changes intrinsic to the NMDA receptor itself. It is possible that altered expression of NMDA receptor subunit genes and splice isoforms of genes leads to subunit combinations resulting in the novel NMDA receptor properties identified in the hippocampus of kindled animals. To begin to address this possibility, we previously examined the hippocampal expression of known NMDA receptor genes and found no differences in expression between control and kindled animals either 24 h or 28 days after the last kindled seizure. Here, we extend that earlier study by examining the expression of NMDAR1 splice isoforms in the hippocampus of control and kindled animals. We report that kindling induces the transient reduction of specific splice isoforms of NMDAR1 containing the first of the carboxy-terminal splice cassettes (exon 21). We discuss the potential significance of this regulation in terms of its relevance to previous findings in the kindling model and possible effects on NMDA receptor function.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Kraus
authors.forename: J V
authors.initials: JV
authors.lastname: Nadler
authors.forename: J O
authors.initials: JO
authors.lastname: McNamara
mesh_terms: D000818:Animals; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate