Mufson E J, Jaffar S, Levey A I
Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
J Comp Neurol. 1998 Mar 16;392(3):313-29.
The distribution of profiles containing the m2-muscarinic acetylcholine receptor within the aged human basal forebrain and its relationship to cholinergic and noncholinerigc neurons and alterations in Alzheimer's disease (AD) was investigated by using an m2-specific monoclonal antibody (Levey et al. [1995] J. Comp. Neurol. 351:339-356). Immunocytochemistry revealed that the m2 receptor protein is expressed primarily in noncholinergic multipolar neurons (mean+/-S.E.M.; 355.7+/-15.4 microm2) located primarily outside the cholinergic nucleus basalis subfields. Dual-stained sections from the septal/diagonal band complex revealed that m2 was detected in only 14% of choline acetyltransferase-labeled neurons, whereas only 13% of m2-stained neurons colocalized choline acetyltransferase. Within the nucleus basalis, choline acetyltransferase was found in 35% of the m2-labeled neurons, whereas only 6% of choline acetyltransferase-stained perikarya were dual labeled for m2. Although we did not visualize colocalization of m2+/choline acetyltransferase-immunonegative neurons and the inhibitory neuropeptide galanin, galaninergic fibers coursed in close apposition to m2+ cells. Cell counts demonstrated that 90% of choline acetyltransferase-labeled striatal neurons expressed the m2 receptor. Despite the extensive reduction in cholinergic basal forebrain neurons, cell counts of the relative number ofm2-immunoreactive neurons within the nucleus basalis complex from aged controls and AD patients revealed that the m2 neurons are spared. Finally, our findings suggest that most m2 receptors in the cholinergic basal forebrain are located on noncholinergic structures; therefore, they are not the major source of m2 receptors in the cortex. Thus, the reduced levels of the m2 receptor seen in AD cortex probably reflect changes in other neuronal populations.
利用一种m2特异性单克隆抗体（Levey等人，[1995]《比较神经学杂志》351:339 - 356），研究了老年人类基底前脑内含有m2 - 毒蕈碱型乙酰胆碱受体的细胞分布情况，及其与胆碱能和非胆碱能神经元的关系以及在阿尔茨海默病（AD）中的变化。免疫细胞化学显示，m2受体蛋白主要表达于主要位于胆碱能基底核亚区之外的非胆碱能多极神经元（平均值±标准误；355.7±15.4平方微米）。来自隔区/斜角带复合体的双重染色切片显示，仅在14%的胆碱乙酰转移酶标记的神经元中检测到m2，而仅13%的m2染色神经元共定位有胆碱乙酰转移酶。在基底核内，35%的m2标记神经元中发现有胆碱乙酰转移酶，而仅6%的胆碱乙酰转移酶染色的核周体同时被m2双重标记。尽管我们未观察到m2 + /胆碱乙酰转移酶免疫阴性神经元与抑制性神经肽甘丙肽的共定位，但甘丙肽能纤维与m2 + 细胞紧密相邻。细胞计数表明，90%的胆碱乙酰转移酶标记的纹状体神经元表达m2受体。尽管胆碱能基底前脑神经元大量减少，但对老年对照和AD患者基底核复合体内m2免疫反应性神经元相对数量的细胞计数显示，m2神经元未受影响。最后，我们的研究结果表明，胆碱能基底前脑中的大多数m2受体位于非胆碱能结构上；因此，它们不是皮质中m2受体的主要来源。因此，AD皮质中m2受体水平的降低可能反映了其他神经元群体的变化。
