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首页> 外文期刊>Brain research >Knockout of sodium pump alpha 3 subunit gene (Atp1a3(-/-)) results in perinatal seizure and defective respiratory rhythm generation
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Knockout of sodium pump alpha 3 subunit gene (Atp1a3(-/-)) results in perinatal seizure and defective respiratory rhythm generation

机译：kegkout of钠泵α3亚基基因（ATP1A3（ - / - ））导致围产期癫痫发作和缺陷呼吸节律发电

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ATP1A3 encodes a neuron-specific human alpha 3 subunit isoform of the sodium pump that plays an important role in neuronal excitability. Point and deletion mutations in ATP1A3 have been recognized in diverse neurological disorders. Three ATP1A3 disorders, alternating hemiplegia of childhood (AHC); apnea; and severe infantile epileptic encephalopathy often appear shortly after birth. To gain insight into the pathophysiology of these disorders and to understand the functional roles of the sodium pump alpha 3 subunit in the brain in vivo during this period of development, we examined the phenotype of Atp1a3 knockout homozygous mouse fetuses (Atp1a3(-/-)). We focused on fetuses just before birth because at birth, about half of them showed severe seizure, and none could continue effective breathing and died soon after birth, without any gross anatomical anomalies. We examined c-Fos expression in the brains of Atp1a3(-/-) and found a significantly increased number of c-Fos-expressing cells in various regions of the brains, with unique distribution in the cerebellum, when compared with wild-type littermates (Atp1a3(+/+)). We also measured contents of monoamine neurotransmitters in the brains and found higher contents, especially of dopamine and noradrenaline, in the brains of Atp1a3(-/-) compared with those of Atp1a3(+/+) In addition, we found various abnormal respiratory rhythms produced in the brainstem of Atp1a3(-/-). These results suggest that Atp1a3 plays a critical role in neural function during development and at birth. (C) 2017 Elsevier B.V. All rights reserved.
机译：ATP1A3编码了钠泵的神经元特异性人α3亚基同源型，其在神经元兴奋性中起重要作用。 ATP1A3中的点和缺失突变已在不同的神经系统障碍中得到识别。三个ATP1A3疾病，儿童的交替偏瘫（AHC）;呼吸暂停;严重的婴儿癫痫脑病通常在出生后不久出现。为了深入了解这些疾病的病理生理学，并在此发育期间了解体内脑内脑中钠泵3亚基的功能作用，我们检查了ATP1A3敲除纯合鼠胎儿的表型（ATP1A3（ - / - ） ）。我们专注于出生前的胎儿，因为出生时，其中大约一半展示了严重的癫痫发作，并且没有任何可能在出生后不久呼吸呼吸，没有任何粗糙的解剖异常。我们在ATP1A3（ - / - ）大脑中检查了C-FOS表达，发现大脑中各个区域中的C-FOS表达细胞数量显着增加，在野生型凋落物相比时，小脑中的独特分布（ATP1A3（+ / +））。我们还在与ATP1A3（+ / +）的大脑中测量了大脑中脑中单胺神经递质的含量，特别是多巴胺和去甲肾上腺素，特别是在ATP1A3（ - / +）的大脑中，我们发现了各种异常呼吸节奏在ATP1A3（ - / - ）的脑干中产生。这些结果表明ATP1A3在开发期间和出生时在神经功能中发挥着关键作用。 （c）2017 Elsevier B.v.保留所有权利。

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