Alpha-7 nicotinic receptor expression by two distinct cell types in the dorsal raphe nucleus and locus coeruleus of rat
Alpha-7 nicotinic receptor expression by two distinct cell types in the dorsal raphe nucleus and locus coeruleus of rat
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DOI：
10.1016/s0006-8993(02)02485-x
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发表时间：
2002-05-31
期刊：
影响因子：
2.9
通讯作者：
Nikkel, AL
中科院分区：
文献类型：
--
作者：
Bitner, RS;Nikkel, AL
α 7烟碱乙酰胆碱受体（nAChR）亚基可以组装形成对钙具有高渗透性的同聚五聚体。尽管已经证明了在整个CNS中α 7-nAChR的表达，但表达α 7的神经元的神经化学表型在很大程度上仍然未知。使用针对α 7 nAChR亚基的抗体，分别在大鼠中缝背核（DRN）和蓝斑（LC）、5-羟色胺能和去甲肾上腺素能脑干核中观察到免疫组织化学染色。在DRN和LC中，似乎存在两种组织学上不同的表达α 7的细胞类型，如通过大小区分的，即大直径与小直径。在用多巴胺能（5，7-二羟色胺）或去甲肾上腺素能（抗多巴胺-β-羟化酶皂草素神经毒素、色氨酸羟化酶和酪氨酸羟化酶）处理的大鼠中，分别取消了免疫染色。同样，α 7阳性大直径细胞不再检测到，表明这些细胞是肾上腺素能DRN和去甲肾上腺素能LC神经元。事实上，双标记实验显示，在大细胞类型的共同表达α 7与色氨酸羟化酶的DRN和酪氨酸羟化酶的LC的盐水处理的大鼠。与大直径细胞相反，α 7阳性的小直径细胞既不是肾上腺素能细胞，也不是肾上腺素能细胞，并且仍然在损伤大鼠的DRN和LC中检测到。此外，细胞计数显示，这些细胞在受损大鼠中的数量增加，在非受损对照中未观察到在体突中表达α 7。双标记揭示了大多数（但不是全部）毒素抗性细胞内α 7和GABA的共表达。这些研究的结果表明，肾上腺素能和去甲肾上腺素能神经元都表达α 7 nAChR。此外，在DRN和LC中似乎都存在小直径细胞类型，可能是GABA能中间神经元，表达可能受神经毒性损伤调节的α 7。(C)2002 Elsevier Science B. V.保留所有权利。
The alpha7 nicotinic acetylcholine receptor (nAChR) subunit can be assembled to form a homomeric-pentamer with high permeability to calcium. Although the expression of the alpha7-nAChR has been demonstrated throughout the CNS, the neurochemical phenotype of neurons expressing alpha7 remains to a large extent unknown. Using an antibody against the alpha7 nAChR subunit, immunohistochemical staining was observed in rat dorsal raphe nucleus (DRN) and locus coeruleus (LC), serotonergic and noradrenergic brainstem nuclei, respectively. In both the DRN and LC, there appeared to be two histologically distinct alpha7-expressing cell types as distinguished by size, i.e. large versus small diameter. In rats treated with either a serotonergic (5,7-dihydroxytryptamine) or noradrenergic (anti-dopamine-beta-hydroxylase saporin neurotoxin, tryptophan hydroxylase and tyrosine hydroxylase immunostaining was abolished, respectively. Similarly, the alpha7-positive large-diameter cells were no longer detectable, suggesting that these cells were serotonergic DRN and noradrenergic LC neurons. Indeed, double-labeling experiments revealed in the large cell types coexpression of alpha7 with tryptophan hydroxylase in the DRN and with tyrosine hydroxylase in the LC of saline-treated rats. In contrast to the large-diameter cells, the alpha7-positive small-diameter cells were neither serotonergic nor adrenergic, and were still detected in both the DRN and LC of lesioned rats. Moreover, cell counts revealed an increase number of these cells in lesioned rats with expression of alpha7 in somal processes not seen in non-lesioned controls. Double labeling revealed coexpression of alpha7 and GABA within the majority, but not all, of the toxin-resistant cells. The results of these studies suggest that both serotonergic and noradrenergic neurons express alpha7 nAChRs. In addition, there appears to be a small-diameter cell-type in both the DRN and LC, possibly a GABAergic interneuron, expressing alpha7 that may be regulated by neurotoxic injury. (C) 2002 Elsevier Science B.V. All rights reserved.