Kv1.1 subunits localize to cardiorespiratory brain networks in mice where their absence induces astrogliosis and microgliosis.

Kv1.1 subunits localize to cardiorespiratory brain networks in mice where their absence induces astrogliosis and microgliosis.
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Kv1.1亚基定位于小鼠的心肺脑网络,其缺失诱导星形胶质细胞增生和小胶质细胞增生。

DOI:
10.1016/j.mcn.2021.103615
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发表时间:
2021-06
影响因子:
3.5
通讯作者:
Glasscock, Edward
Glasscock, Edward
中科院分区:
医学3区
文献类型:
--
作者:
Dhaibar, Hemangini A.;Hamilton, Kathryn A.;Glasscock, Edward

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癫痫发作后的心肺衰竭是癫痫猝死(SUDEP)的疑似原因,而癫痫猝死是癫痫相关死亡的主要原因。在常用的Kcna 1基因敲除(Kcna 1 −/−)小鼠SUDEP模型中,心肺功能分析揭示了一系列异常呼吸模式,这些模式可能导致与糖尿病相关的死亡风险。然而,介导这些呼吸异常的大脑结构仍然未知。我们假设大脑呼吸控制中心的Kv1.1缺陷导致Kcna 1 −/−小鼠呼吸功能障碍,导致SUDEP风险增加。因此,在这项研究中,我们首先使用免疫组织化学映射Kv1.1蛋白在野生型Kcna 1 +/+(WT)小鼠心肺脑区的表达。接下来,GFAP和Iba 1免疫染色分别用于检测Kcna 1 −/−小鼠心肺中心是否存在星形胶质细胞增生和小胶质细胞增生,这可能表明与呼吸相关的脑损伤可能会损害呼吸。在WT型小鼠中,我们检测到Kv1.1蛋白在所有心肺中心检查,包括基底外侧杏仁核,背侧呼吸组,迷走神经背侧运动核,疑核,腹侧呼吸柱,脑桥呼吸组,以及化学感觉中心,包括后斜方核和中缝核。在Kcna 1 −/−小鼠的相同区域观察到广泛的神经胶质增生,这表明脑损伤相关的脑损伤可能导致呼吸异常。
Cardiorespiratory collapse following a seizure is a suspected cause of sudden unexpected death in epilepsy (SUDEP), the leading cause of epilepsy-related mortality. In the commonly used Kcna1 gene knockout (Kcna1−/−) mouse model of SUDEP, cardiorespiratory profiling reveals an array of aberrant breathing patterns that could contribute to risk of seizure-related mortality. However, the brain structures mediating these respiratory abnormalities remain unknown. We hypothesize that Kv1.1 deficiency in respiratory control centers of the brain contribute to respiratory dysfunction in Kcna1−/− mice leading to increased SUDEP risk. Thus, in this study, we first used immunohistochemistry to map expression of Kv1.1 protein in cardiorespiratory brain regions of wild-type Kcna1+/+ (WT) mice. Next, GFAP and Iba1 immunostaining was used to test for the presence of astrogliosis and microgliosis, respectively, in the cardiorespiratory centers of Kcna1−/− mice, which could be indicative of seizure-related brain injury that could impair breathing. In WT type mice, we detected Kv1.1 protein in all cardiorespiratory centers examined, including the basolateral amygdala, dorsal respiratory group, dorsal motor nucleus of vagus, nucleus ambiguus, ventral respiratory column, and pontine respiratory group, as well as chemosensory centers including the retrotrapezoid and median raphae nuclei. Extensive gliosis was observed in the same areas in Kcna1−/− mice suggesting that seizure-associated brain injury could contribute to respiratory abnormalities.
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