Abstract:
:De novo heterozygous mutations in the STX1B gene, encoding syntaxin 1B, cause a familial, fever-associated epilepsy syndrome. Syntaxin 1B is an essential component of the pre-synaptic neurotransmitter release machinery as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein that regulates the exocytosis of synaptic vesicles. It is also involved in regulating the functions of the SLC6 family of neurotransmitter transporters that reuptake neurotransmitters, including inhibitory neurotransmitters, such as γ-aminobutyric acid (GABA) and glycine. The purpose of the present study was to elucidate the molecular mechanisms underlying the development of febrile seizures by examining the effects of syntaxin 1B haploinsufficiency on inhibitory synaptic transmission during hyperthermia in a mouse model. Stx1b gene heterozygous knockout (Stx1b+/- ) mice showed increased susceptibility to febrile seizures and drug-induced seizures. In cultured hippocampal neurons, we examined the temperature-dependent properties of neurotransmitter release and reuptake by GABA transporter-1 (GAT-1) at GABAergic neurons using whole-cell patch-clamp recordings. The rate of spontaneous quantal GABA release was reduced in Stx1b+/- mice. The hyperthermic temperature increased the tonic GABAA current in wild-type (WT) synapses, but not in Stx1b+/- synapses. In WT neurons, recurrent bursting activities were reduced in a GABA-dependent manner at hyperthermic temperature; however, this was abolished in Stx1b+/- neurons. The blockade of GAT-1 increased the tonic GABAA current and suppressed recurrent bursting activities in Stx1b+/- neurons at the hyperthermic temperature. These data suggest that functional abnormalities associated with GABA release and reuptake in the pre-synaptic terminals of GABAergic neurons may increase the excitability of the neural circuit with hyperthermia.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Mishima T,Fujiwara T,Kofuji T,Saito A,Terao Y,Akagawa Kdoi
10.1111/jnc.15159subject
Has Abstractpub_date
2020-08-28 00:00:00eissn
0022-3042issn
1471-4159pub_type
杂志文章abstract::Focal brain ischemia leads to a slow type of neuronal death in the penumbra that starts several hours after ischemia and continues to mature for days. During this maturation period, blood flow, cellular ATP and ionic homeostasis are gradually recovered in the penumbral region. In striking contrast, protein synthesis i...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2006-07-01 00:00:00
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journal_title:Journal of neurochemistry
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更新日期:2010-06-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb08125.x
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doi:10.1111/j.1471-4159.2011.07345.x
更新日期:2011-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67010186.x
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1981-04-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:2004-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1987-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2003.02332.x
更新日期:2004-04-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07577.x
更新日期:2012-01-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2007.04479.x
更新日期:2007-07-01 00:00:00
abstract::The myelin-deficient (mld) mouse is an autosomal recessive mutant characterized by hypomyelination of the CNS due to reduced expression of the myelin basic protein (MBP) gene. In the mld mutant, the MBP gene is duplicated in tandem. One gene is intact, but a large portion is inverted upstream of the other copy, and it...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
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更新日期:1991-02-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06661.x
更新日期:2010-05-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2005-04-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1985.tb04076.x
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb04168.x
更新日期:1990-08-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12013
更新日期:2012-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/jnc.15224
更新日期:2020-10-26 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12137
更新日期:2013-03-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 评论,社论
doi:10.1111/jnc.14156
更新日期:2017-12-01 00:00:00
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journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03261.x
更新日期:2005-08-01 00:00:00