Maintenance of the Innate Seizure Threshold by Cyclooxygenase-2 is Not Influenced by the Translational Silencer, T-cell Intracellular Antigen-1.
Maintenance of the Innate Seizure Threshold by Cyclooxygenase-2 is Not Influenced by the Translational Silencer, T-cell Intracellular Antigen-1.
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DOI：
10.1016/j.neuroscience.2018.01.004
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发表时间：
2018-03-01
期刊：
影响因子：
3.3
通讯作者：
Hewett JA
中科院分区：
文献类型：
--
作者：
Gong Y;Hewett JA
神经元环氧化酶-2 （COX-2）是正常大脑中PG合成的主要来源，其活性通过兴奋性神经传递而增强，这被认为与癫痫发作抑制有关。本研究结果显示，在神经元中过度表达COX-2的转基因小鼠中，戊四唑（PTZ）诱导的惊厥发生率受到抑制，这支持了这一观点。t细胞胞内抗原-1 （TIA-1）是一种mRNA结合蛋白，已知在非神经元细胞类型中与COX-2 mRNA结合并抑制其翻译。对正常大脑中TIA-1蛋白表达谱的检查表明，它在神经元中广泛表达，包括那些表达COX-2的神经元。然而，TIA-1是否调节神经元中COX-2蛋白水平尚不清楚。本研究的目的是测试TIA-1缺失是否会增加神经元中COX-2的表达，从而提高癫痫发作阈值。结果表明，在缺乏功能性Tia1基因的小鼠中，COX-2的基础表达谱和癫痫诱导的表达谱都没有改变，这表明TIA-1不参与调节神经元中COX-2蛋白的表达。在缺乏TIA-1蛋白的小鼠中，ptz诱导的急性癫痫发作阈值也没有变化，表明这种混杂的RNA结合蛋白不影响先天癫痫发作阈值。然而，这些结果提高了神经元COX-2表达水平可能是先天癫痫阈值的决定因素的可能性，并表明更好地了解大脑中COX-2表达的调控可以为抑制癫痫诱导的分子机制提供新的见解。
Activity of neuronal cyclooxygenase-2 (COX-2), a primary source of PG synthesis in the normal brain, is enhanced by excitatory neurotransmission and this is thought to be involved in seizure suppression. Results herein showing that the incidence of pentylenetetrazole (PTZ)-induced convulsions is suppressed in transgenic mice overexpressing COX-2 in neurons supports this notion. T-cell intracellular antigen-1 (TIA-1) is an mRNA binding protein that is known to bind to COX-2 mRNA and repress its translation in non-neuronal cell types. An examination of the expression profile of TIA-1 protein in the normal brain indicated that it is expressed broadly by neurons, including those that express COX-2. However, whether TIA-1 regulates COX-2 protein levels in neurons is not known. The purpose of this study was to test the possibility that deletion of TIA-1 increases COX-2 expression in neurons and consequently raises the seizure threshold. Results demonstrate that neither the basal nor seizure-induced expression profiles of COX-2 were altered in mice lacking a functional Tia1 gene suggesting that TIA-1 does not contribute to regulation of COX-2 protein expression in neurons. The acute PTZ-induced seizure threshold was also unchanged in mice lacking TIA-1 protein, indicating that this promiscuous RNA binding protein does not influence the innate seizure threshold. Nevertheless, the results raise the possibility that the level of neuronal COX-2 expression may be a determinant of the innate seizure threshold and suggest that a better understanding of the regulation of COX-2 expression in the brain could provide new insight into the molecular mechanisms that suppress seizure induction.
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影响因子：
2.9
作者：
FORSTERMANN, U;HELDT, R;HERTTING, G
通讯作者：
HERTTING, G
影响因子：
4.8
作者：
Cok, SJ;Acton, SJ;Morrison, AR
通讯作者：
Morrison, AR
影响因子：
4.8
作者：
Dixon, DA;Kaplan, CD;Prescott, SM
通讯作者：
Prescott, SM
影响因子：
64.5
作者：
AIGNER, L;ARBER, S;CARONI, P
通讯作者：
CARONI, P
DOI：
10.1084/jem.20030616
发表时间：
2003-08-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dixon DA;Balch GC;Kedersha N;Anderson P;Zimmerman GA;Beauchamp RD;Prescott SM
通讯作者：
Prescott SM