Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons
Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons
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DOI：
10.1002/cne.10138
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发表时间：
2002-03-12
影响因子：
2.5
通讯作者：
Leslie, FM
中科院分区：
文献类型：
--
作者：
Azam, L;Winzer-Serhan, UH;Leslie, FM
尼古丁的许多行为效应是黑质纹状体和中脑边缘多巴胺能系统激活的结果。尼古丁不仅通过刺激黑质和腹侧被盖区(SN/VTA)多巴胺细胞体上的烟碱型乙酰胆碱受体(NAChRs)来调节多巴胺的释放，而且还通过刺激位于纹状体终末的突触前nAChRs来调节多巴胺的释放。细胞体和终末的nAChR亚型(S)仍然存在争议。本研究的目的是用地高辛标记的酪氨酸羟基酶核糖核酸探针和S-35标记的核糖核酸探针，用双标记原位杂交法鉴定黑质/室旁核多巴胺神经元中表达的nAChR亚单位mRNAs。结果显示，在中脑多巴胺神经元中，nAChR亚单位mRNAs的数量是不同的。在黑质内，几乎所有的多巴胺神经元都表达α2、α4、α5、α6、β2和β3nAChR mRNAs，超过一半的神经元还表达alpha3和alpha7mRNAs。相比之下，不到10%的人表达Beta4mRNA。在VTA内，可以观察到类似的nAChR亚单位mRNA表达模式，只是大多数亚单位在多巴胺神经元中的表达比例略低于SN。在黑质内，α4、β2、α7和β4mRNAs也在相当数量的非多巴胺能神经元中表达，而在VTA内，这只在Beta4中表达。SN/VTA内nAChR亚基表达的异质性可能表明在黑质纹状体和中脑边缘通路的细胞体和终末上形成了多种不同的nAChR亚型。J.Comp.神经。444：260-274,2002。(C)2002年Wiley-Liss，Inc.
Many behavioral effects of nicotine result from activation of nigrostriatal and mesolimbic dopaminergic systems. Nicotine regulates dopamine release not only by stimulation of nicotinic acetylcholine receptors (nAChRs) on dopamine cell bodies within the substantia nigra and ventral tegmental area (SN/VTA), but also on presynaptic nAChRs located on striatal terminals. The nAChR subtype(s) present on both cell bodies and terminals is still a matter of controversy. The purpose of this study was to use double-labeling in situ hybridization to identify nAChR subunit mRNAs expressed within dopamine neurons of the SN/VTA, by using a digoxigenin-labeled riboprobe for tyrosine hydroxylase as the dopamine cell marker and S-35-labeled riboprobes for nAChR subunits. The results reveal a heterogeneous population of nAChR subunit mRNAs within midbrain dopamine neurons. Within the SN, almost all dopamine neurons express alpha2, alpha4, alpha5, alpha6, beta2, and beta3 nAChR mRNAs, with more than half also expressing alpha3 and alpha7 mRNAs. In contrast, less than 10% express beta4 mRNA. Within the VTA, a similar pattern of nAChR subunit mRNA expression is observed except that most subunits are expressed in a slightly lower percentage of dopamine neurons than in the SN. Within the SN, alpha4, beta2, alpha7, and beta4 mRNAs are also expressed in a significant number of nondopaminergic neurons, whereas within the VTA this only occurs for beta4. The heterogeneity in the expression of nAChR subunits within the SN/VTA may indicate the formation of a variety of different nAChR subtypes on cell bodies and terminals of the nigrostriatal and mesolimbic pathways. J. Comp. Neurol. 444:260-274, 2002. (C) 2002 Wiley-Liss, Inc.