Expression of Calretinin Among Different Neurochemical Classes of Interneuron in the Superficial Dorsal Horn of the Mouse Spinal Cord
Expression of Calretinin Among Different Neurochemical Classes of Interneuron in the Superficial Dorsal Horn of the Mouse Spinal Cord
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DOI：
10.1016/j.neuroscience.2018.12.009
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发表时间：
2019-02-01
期刊：
影响因子：
3.3
通讯作者：
Todd, Andrew J.
中科院分区：
文献类型：
--
作者：
Gutierrez-Mecinas, Maria;Davis, Olivia;Todd, Andrew J.
小鼠背角 I-II 层中约 75% 的神经元是兴奋性中间神经元，这些神经元是正常疼痛感知所必需的。我们已经证明，四个基本上不重叠的兴奋性中间神经元群体可以通过神经肽神经降压素、神经激肽 B (NKB)、胃泌素释放肽 (GRP) 和 P 物质的表达来定义。此外，我们最近在无毛皮肤区域中发现了表达强啡肽的兴奋性中间神经元群体。钙结合蛋白钙结合蛋白存在于该区域的许多兴奋性神经元中，但我们对其与这些神经肽标记物的关系知之甚少。在这里，我们发现钙结合蛋白存在差异表达，存在于大多数表达 P 物质、GRP 和 NKB 的细胞中，但不存在于神经降压素或强啡肽细胞中。钙结合蛋白阳性细胞与有害机械刺激的检测有关，但对于神经性疼痛后的触觉异常性疼痛来说并不需要。因此，我们的研究结果与神经性异常性疼痛涉及神经降压素和/或强啡肽兴奋性中间神经元群体的建议一致。 I-II 层中大约四分之一的抑制性中间神经元含有钙结合蛋白，最近的转录组学研究表明这些共表达物质 P。我们通过证明 Tac1(Cre) 敲入小鼠中的抑制性 Cre 表达细胞具有钙结合蛋白免疫反应性来证实这一点。有趣的是，有证据表明这些细胞表达低水平的肽基甘氨酸α-酰胺化单加氧酶，这是神经肽成熟所需的酶。这可能解释了我们之前的发现，即虽然在一些抑制性中间神经元中可以检测到 P 物质前体前原速激肽 A，但很少有抑制性轴突布顿对 P 物质具有免疫反应性。(C) 2018 作者。由 Elsevier Ltd 代表 IBRO 出版。
Around 75% of neurons in laminae I-II of the mouse dorsal horn are excitatory interneurons, and these are required for normal pain perception. We have shown that four largely non-overlapping excitatory interneuron populations can be defined by expression of the neuropeptides neurotensin, neurokinin B (NKB), gastrin-releasing peptide (GRP) and substance P. In addition, we recently identified a population of excitatory interneurons in glabrous skin territory that express dynorphin. The calcium-binding protein calretinin is present in many excitatory neurons in this region, but we know little about its relation to these neuropeptide markers. Here we show that calretinin is differentially expressed, being present in the majority of substance P-, GRP- and NKB-expressing cells, but not in the neurotensin or dynorphin cells. Calretinin-positive cells have been implicated in detection of noxious mechanical stimuli, but are not required for tactile allodynia after neuropathic pain. Our findings are therefore consistent with the suggestion that neuropathic allodynia involves the neurotensin and/or dynorphin excitatory interneuron populations. Around a quarter of inhibitory interneurons in lamina I-II contain calretinin, and recent transcriptomic studies suggest that these co-express substance P. We confirm this, by showing that inhibitory Cre-expressing cells in a Tac1(Cre) knock-in mouse are calretinin-immunoreactive. Interestingly, there is evidence that these cells express low levels of peptidylglycine alpha-amidating monooxygenase, an enzyme required for maturation of neuropeptides. This may explain our previous finding that although the substance P precursor preprotachykinin A can be detected in some inhibitory interneurons, very few inhibitory axonal boutons are immunoreactive for substance P. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of IBRO.