Chan-Palay V, Höchli M, Savaskan E, Hungerecker G
Neurology Clinic, University Hospital, Zurich, Switzerland.
Dementia. 1993 Jan-Feb;4(1):1-15. doi: 10.1159/000107290.
In this study, calbindin D-28k (CaBP), monoamine oxidase A (MAO A) and nerve growth factor receptor (NGFr) immunoreactivities were investigated in the nucleus basalis of Meynert (NbM) in patients with senile dementia of the Alzheimer type (SDAT), with Parkinson's disease (PD) with or without dementia, and in controls. Immunocytochemistry using specific antibodies in differing serial sections was employed, and cell counts and NbM nuclear volume measurements were made. Most of the large multipolar NbM neurons showed CaBP immunoreactivity in the cytoplasm of their somata, dendrites and axons. In adjacent, NGFr-reacted sections, the large NbM neurons were also found to be intensely immunoreactive for NGFr on their cellular surfaces. In addition, a subpopulation of large NbM neurons and glial cells were found to be immunoreactive for MAO A. The number of CaBP-immunoreactive (CaBP-i) neurons was decreased by an average of 55% in the 6 SDAT patients, 70% in the 2 nondemented PD patients and 40% in the 1 demented PD patient. The volume calculated for the compact part of the NbM formed by the CaBP-i neuronal somata decreased by an average of 47% in SDAT. On the other hand, measurements in the volume of NGFr-i neurons (including the dendritic arborization) showed an average decrease of 25% in SDAT patients compared to controls. Although all SDAT and PD patients showed a decrease of CaBP-i neurons in the NbM, a loss of MAO-A-i NbM neurons was found only in those patients with dementia. Therefore, the relative proportions of MAO-A-i to CaBP-i neurons were increased in the nondemented PD patients (14.2 and 19.6%) when compared with those in the demented PD patient (2.2%) and with the SDAT patients (0.3-5.6%). These data indicate that a balanced presence of MAO-A-i cholinergic, large NbM neurons may be necessary for the proper maintenance of cognitive function. Functionally this may be translated to mean that dementing changes may cause a decrease from the normal amount of MAO A enzyme activity. This suggests that therapeutic strategies based upon correction of MAO-A activities by MAO-A inhibitors may be important to ameliorating some of the loss in cholinergic function in dementias of SDAT and PD.
在本研究中，我们调查了阿尔茨海默型老年痴呆症（SDAT）患者、伴有或不伴有痴呆的帕金森病（PD）患者以及对照组患者Meynert基底核（NbM）中钙结合蛋白D-28k（CaBP）、单胺氧化酶A（MAO A）和神经生长因子受体（NGFr）的免疫反应性。我们采用在不同连续切片中使用特异性抗体的免疫细胞化学方法，并进行细胞计数和NbM核体积测量。大多数大型多极NbM神经元在其胞体、树突和轴突的细胞质中显示出CaBP免疫反应性。在相邻的NGFr反应切片中，大型NbM神经元在其细胞表面也被发现对NGFr有强烈的免疫反应性。此外，发现大型NbM神经元和神经胶质细胞的一个亚群对MAO A有免疫反应性。6例SDAT患者中，CaBP免疫反应性（CaBP-i）神经元数量平均减少55%；2例非痴呆PD患者中减少70%；1例痴呆PD患者中减少40%。由CaBP-i神经元胞体形成的NbM致密部分的计算体积在SDAT中平均减少47%。另一方面，与对照组相比，SDAT患者中NGFr-i神经元（包括树突分支）体积测量显示平均减少25%。尽管所有SDAT和PD患者的NbM中CaBP-i神经元均减少，但仅在痴呆患者中发现MAO-A-i NbM神经元丢失。因此，与痴呆PD患者（2.2%）和SDAT患者（0.3 - 5.6%）相比，非痴呆PD患者中MAO-A-i与CaBP-i神经元的相对比例增加（分别为14.2%和19.6%）。这些数据表明，MAO-A-i胆碱能大型NbM神经元的平衡存在可能是认知功能正常维持所必需的。在功能上，这可能意味着痴呆性改变可能导致MAO A酶活性从正常水平下降。这表明基于MAO-A抑制剂纠正MAO-A活性的治疗策略对于改善SDAT和PD痴呆中胆碱能功能的一些损失可能很重要。
