The Role of Kainate Receptors in the Pathophysiology of Hypoxia-Induced Seizures in the Neonatal Mouse.
The Role of Kainate Receptors in the Pathophysiology of Hypoxia-Induced Seizures in the Neonatal Mouse.
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DOI：
10.1038/s41598-018-24722-3
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发表时间：
2018-05-04
影响因子：
4.6
通讯作者：
Zanelli SA
中科院分区：
文献类型：
--
作者：
Grosenbaugh DK;Ross BM;Wagley P;Zanelli SA
盐酸盐受体（KARs）是谷氨酸受体，在胚胎晚期和出生后早期表达高峰。在包括癫痫在内的几种脑部疾病中观察到kar介导的神经传递和亚基表达的改变。在这里，我们研究了KARs在调节缺氧损伤新生C57BL/6小鼠癫痫发作中的作用。我们发现敲除GluK2亚基或UBP310阻断KARs可降低再氧化期间癫痫发作的易感性。在缺氧损伤后，我们观察到海马CA3锥体细胞的兴奋性神经传递增加，在缺氧前用UBP310治疗可以阻断这一过程。同样，我们在体外缺氧缺血海马切片模型中观察到CA3锥体细胞的兴奋性神经传递增加。这种增加在GluK2 - / -小鼠和UBP310处理的切片中不存在，这表明KARs至少在一定程度上调节新生小鼠体内缺氧后的兴奋性突触神经传递。这些缺氧模型的数据表明，KARs，特别是那些含有GluK2亚基的KARs，有助于新生小鼠兴奋性神经传递和癫痫易感性的改变，特别是在再氧合期间。以KARs为目标的治疗方法可能在治疗受缺氧发作影响的新生儿中取得成功。
Kainate receptors (KARs) are glutamate receptors with peak expression during late embryonic and early postnatal periods. Altered KAR-mediated neurotransmission and subunit expression are observed in several brain disorders, including epilepsy. Here, we examined the role of KARs in regulating seizures in neonatal C57BL/6 mice exposed to a hypoxic insult. We found that knockout of the GluK2 subunit, or blockade of KARs by UBP310 reduced seizure susceptibility during the period of reoxygenation. Following the hypoxic insult, we observed an increase in excitatory neurotransmission in hippocampal CA3 pyramidal cells, which was blocked by treatment with UBP310 prior to hypoxia. Similarly, we observed increased excitatory neurotransmission in CA3 pyramidal cells in an in vitro hippocampal slice model of hypoxic-ischemia. This increase was absent in slices from GluK2−/− mice and in slices treated with UBP310, suggesting that KARs regulate, at least in part, excitatory synaptic neurotransmission following in vivo hypoxia in neonatal mice. Data from these hypoxia models demonstrate that KARs, specifically those containing the GluK2 subunit, contribute to alterations in excitatory neurotransmission and seizure susceptibility, particularly during the reoxygenation period, in neonatal mice. Therapies targeting KARs may prove successful in treatment of neonates affected by hypoxic seizures.
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影响因子：
3.6
作者：
Atlason, Palmi T.;Scholefield, Caroline L.;Molnar, Elek
通讯作者：
Molnar, Elek
影响因子：
4
作者：
Fisher, Janet L.;Housley, Paul R.
通讯作者：
Housley, Paul R.
DOI：
10.2201/nonlin.003.01.002
发表时间：
2005-01-01
期刊：
Nonlinearity in Biology Toxicology and Medicine
影响因子：
--
作者：
Baldi, Elisabetta;Bucherelli, Corrado
通讯作者：
Bucherelli, Corrado
影响因子：
3.3
作者：
Das, A.;Wallace, G. C.;Holmes, C.;McDowell, M. L.;Smith, J. A.;Marshall, J. D.;Bonilha, L.;Edwards, J. C.;Glazier, S. S.;Ray, S. K.;Banik, N. L.
通讯作者：
Banik, N. L.
影响因子：
4.4
作者：
Grigorenko, E;Glazier, S;Deadwyler, SA
通讯作者：
Deadwyler, SA