Aubert I, Cécyre D, Gauthier S, Quirion R
Douglas Hospital Research Centre, Verdun, Quebec, Canada.
J Comp Neurol. 1996 May 20;369(1):31-55. doi: 10.1002/(SICI)1096-9861(19960520)369:1<31::AID-CNE3>3.0.CO;2-L.
The ontogenic profiles of several cholinergic markers were assessed in the rat brain by using quantitative in vitro receptor autoradiography. Brain sections from animals at different stages of development were processed with [3H]AH5183 (vesamicol; vesicular acetylcholine transport sites), [3H]N-methylcarbamylcholine (alpha(4)beta(2) nicotinic receptor sites), [3H]hemicholinium-3 (high-affinity choline uptake sites), [3H]3-quinuclidinyl benzilate (total population of muscarinic receptor sites), [3H]4-DAMP (muscarinic M1/M3 receptor sites), [3H]pirenzepine (muscarinic M1 receptor sites), and [3H]AF-DX 116 and [3H]AF-DX 384 (muscarinic M2 receptor sites) as radiolabeled probes. The results revealed that, by the end of the prenatal period (embryonic day 20), the densities of nicotinic receptor and vesicular acetylcholine transport sites already represented a considerable proportion of those observed in adulthood (postnatal day 60) in different laminae of the frontal, parietal, and occipital cortices, in the layers of Ammon's horn fields and the dentate gyrus of the hippocampal formation, as well as in the amygdaloid body, the olfactory tubercle, and the striatum. In contrast, at that stage, the densities of total muscarinic, M1/M3, M1, and possibly M2 receptor and high-affinity choline uptake sites represent only a small proportion of levels seen in the adult. Differences were also observed in the postnatal ontogenic profiles of nicotinic, muscarinic, vesamicol, and high-affinity choline uptake sites. For example, between postnatal weeks 3 and 5, the levels of M1/M3 and M1 sites were at least as high as in the adult, whereas M2 and high-affinity choline uptake site densities appeared to be delayed and to reach adult values only after postnatal week 5. With regard to cholinergic innervation in the developing rat brain, the present findings suggest a temporal establishment of several components of the cholinergic systems. The first components are the vesicular acetylcholine transporter and nicotinic sites; these are followed by M1/M3 and M1 sites and, finally, by M2 and high-affinity choline uptake sites.
通过定量体外受体放射自显影技术评估了大鼠脑中几种胆碱能标志物的个体发育情况。用[3H]AH5183（vesamicol；囊泡乙酰胆碱转运位点）、[3H]N - 甲基氨甲酰胆碱（α(4)β(2)烟碱样受体位点）、[3H]半胱氨酸-3（高亲和力胆碱摄取位点）、[3H]3 - 喹核醇苯甲酸酯（毒蕈碱样受体位点总数）、[3H]4 - DAMP（毒蕈碱样M1/M3受体位点）、[3H]哌仑西平（毒蕈碱样M1受体位点）以及[3H]AF - DX 116和[3H]AF - DX 384（毒蕈碱样M2受体位点）作为放射性标记探针，对处于不同发育阶段动物的脑切片进行处理。结果显示，在产前阶段结束时（胚胎第20天），烟碱样受体和囊泡乙酰胆碱转运位点的密度在额叶、顶叶和枕叶皮质的不同层、海马结构的海马角层和齿状回、杏仁体、嗅结节以及纹状体中，已占成年期（出生后第60天）观察值的相当比例。相比之下，在该阶段，毒蕈碱样受体总数、M1/M3、M1以及可能的M2受体和高亲和力胆碱摄取位点的密度仅占成年期水平的一小部分。在烟碱样、毒蕈碱样、vesamicol和高亲和力胆碱摄取位点的出生后个体发育情况中也观察到了差异。例如，在出生后第3周和第5周之间，M1/M3和M1位点的水平至少与成年期一样高，而M2和高亲和力胆碱摄取位点的密度似乎延迟出现，并且仅在出生后第5周后才达到成年值。关于发育中大鼠脑内的胆碱能神经支配，目前的研究结果表明胆碱能系统的几个组成部分是按时间顺序建立的。首先是囊泡乙酰胆碱转运体和烟碱样位点；其次是M1/M3和M1位点，最后是M2和高亲和力胆碱摄取位点。
