Breese C R, Adams C, Logel J, Drebing C, Rollins Y, Barnhart M, Sullivan B, Demasters B K, Freedman R, Leonard S
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
J Comp Neurol. 1997 Oct 27;387(3):385-98. doi: 10.1002/(sici)1096-9861(19971027)387:3<385::aid-cne5>3.0.co;2-x.
Neuronal nicotinic acetylcholine receptors are expressed in the human central nervous system. A specific subtype of this receptor family, the alpha7 nicotinic acetylcholine receptor, is thought to be the principal alpha-bungarotoxin (alphaBTX)-binding protein in mammalian brain. Although the expression of this receptor subtype has been characterized in rat, no study has specifically compared the expression of both the alpha7 gene and the localization of BTX binding sites in human brain. Expression of alpha7 mRNA and receptor protein in human postmortem brain tissue was examined by in situ hybridization and [125I]-alpha-bungarotoxin autoradiography, respectively, with particular emphasis on regions associated with sensory processing. Regions with high levels of both alpha7 gene expression and [125I]-alphaBTX binding include the nucleus reticularis of the thalamus, the lateral and medial geniculate bodies, the basilar pontine nucleus, the horizontal limb of the diagonal band of Broca, the nucleus basalis of Meynert, and the inferior olivary nucleus. High-to-moderate levels of alpha7 probe hybridization were also seen in the hippocampus and the cerebral cortex; however, there was a reduced or variable degree of [125I]-alphaBTX binding in these regions compared with the level of probe hybridization. In most brain regions, [125I]-alphaBTX binding was localized to neuronal cell bodies similar in morphology to those that exhibited alpha7 hybridization, suggesting that the high-affinity [125I]-alphaBTX binding sites in the human brain are likely to be principally composed of alpha7 receptor subtypes.
神经元烟碱型乙酰胆碱受体在人类中枢神经系统中表达。该受体家族的一种特定亚型,即α7烟碱型乙酰胆碱受体,被认为是哺乳动物脑中主要的α-银环蛇毒素(αBTX)结合蛋白。尽管该受体亚型的表达已在大鼠中得到表征,但尚无研究专门比较人脑中α7基因的表达和BTX结合位点的定位。分别通过原位杂交和[125I]-α-银环蛇毒素放射自显影术检测了人死后脑组织中α7 mRNA和受体蛋白的表达,特别关注与感觉处理相关的区域。α7基因表达和[125I]-αBTX结合水平较高 的区域包括丘脑网状核、外侧和内侧膝状体、脑桥基底核、布洛卡斜带水平支、迈内特基底核和下橄榄核。在海马体和大脑皮层中也观察到α7探针杂交水平为高到中度;然而,与探针杂交水平相比,这些区域中[125I]-αBTX结合程度降低或存在差异。在大多数脑区,[125I]-αBTX结合定位于形态与显示α7杂交的神经元细胞体相似的神经元细胞体,这表明人脑中高亲和力的[125I]-αBTX结合位点可能主要由α7受体亚型组成。