Conserved interneuron-specific ErbB4 expression in frontal cortex of rodents, monkeys, and humans: implications for schizophrenia.
Conserved interneuron-specific ErbB4 expression in frontal cortex of rodents, monkeys, and humans: implications for schizophrenia.
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DOI：
10.1016/j.biopsych.2011.04.016
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发表时间：
2011-10-01
影响因子：
10.6
通讯作者：
Buonanno, Andres
中科院分区：
文献类型：
--
作者：
Neddens, Joerg;Fish, Kenneth N.;Tricoire, Ludovic;Vullhorst, Detlef;Shamir, Alon;Chung, Wonjae;Lewis, David A.;McBain, Chris J.;Buonanno, Andres
关键词：
Neuregulin-1 和 ErbB4 在遗传上与精神分裂症相关，详细了解 ErbB4 的细胞和亚细胞定位对于理解 neuregulin-1 如何调节神经元网络活动和行为非常重要。 ErbB4 的表达仅限于啮齿动物海马和皮层的中间神经元。然而，关于灵长类动物大脑中的细胞表达模式及其在突触后体树突位置与突触前末梢的亚细胞分布仍然存在争议。对五个物种额叶皮层的锥体细胞和中间神经元中的 ErbB4 表达进行了分析：C57BL6 小鼠 (n = 3)、ErbB4−/− 小鼠 (n = 2)、Sprague-Dawley 大鼠 (n = 3)、两种猕猴 (n = 3 + 2) 和人类（正常对照受试者，n = 2）。我们研究了 1) 小鼠、猕猴和人类的信使 RNA； 2) 使用高度特异性的单克隆抗体在所有物种中进行蛋白质表达； 3) 几种 ErbB4 抗体对脑样本（小鼠、猕猴、人）的特异性测试。 ErbB4 RNA 仅限于小鼠额叶皮层的中间神经元。 ErbB4 蛋白在啮齿动物、猕猴和人类额叶皮层的锥体细胞中检测不到，而大多数中间神经元对小白蛋白、钙结合蛋白或胆囊收缩素呈阳性，但只有少数钙结合蛋白阳性细胞在猕猴中共表达 ErbB4。重要的是，在任何物种中均未检测到突触前 ErbB4 表达。 ErbB4 的中间神经元选择性体细胞树突表达与神经调节蛋白-ErbB4 信号在啮齿动物和灵长类动物中 γ-氨基丁酸能功能的突触后调节中的主要作用一致。我们的数据验证了使用啮齿动物来分析异常 ErbB4 功能的影响作为模拟精神疾病内表型的一种手段。
Neuregulin-1 and ErbB4 are genetically associated with schizophrenia, and detailed knowledge of the cellular and subcellular localization of ErbB4 is important for understanding how neuregulin-1 regulates neuronal network activity and behavior. Expression of ErbB4 is restricted to interneurons in the rodent hippocampus and cortex. However, controversy remains about the cellular expression pattern in primate brain and its subcellular distribution in postsynaptic somatodendritic locations versus presynaptic terminals. ErbB4 expression was analyzed in pyramidal cells and interneurons in the frontal cortex of five species: C57BL6 mice (n = 3), ErbB4−/− mice (n = 2), Sprague-Dawley rats (n = 3), two macaque species (n = 3 + 2), and humans (normal control subjects, n = 2). We investigated 1) messenger RNA in mice, macaques, and humans; 2) protein expression in all species using highly specific monoclonal antibodies; and 3) specificity tests of several ErbB4 antibodies on brain samples (mouse, macaque, human). ErbB4 RNA is restricted to interneurons in the frontal cortex of mice. ErbB4 protein is undetectable in pyramidal cells of rodents, macaques, and human frontal cortex, whereas most interneurons positive for parvalbumin, calretinin, or cholecystokinin, but only a minority of calbindin-positive cells, co-express ErbB4 in macaques. Importantly, no presynaptic ErbB4 expression was detected in any species. The interneuron-selective somatodendritic expression of ErbB4 is consistent with a primary role of neuregulin-ErbB4 signaling in the postsynaptic modulation of gamma-aminobutyric acidergic function in rodents and primates. Our data validate the use of rodents to analyze effects of abnormal ErbB4 function as a means to model endophenotypes of psychiatric disorders.
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影响因子：
3.8
作者：
Buonanno A
通讯作者：
Buonanno A
影响因子：
16.2
作者：
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通讯作者：
Mei, L
DOI：
10.1073/pnas.1010669107
发表时间：
2010-12-14
影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Carroll, SL