Ishunina Tatjana A, Fisser Bart, Swaab Dick F
Netherlands Institute for Brain Research, Amsterdam, The Netherlands.
Exp Neurol. 2002 Jul;176(1):122-32. doi: 10.1006/exnr.2002.7907.
The vertical limb of the diagonal band of Broca (VDB or Ch2) and the nucleus basalis of Meynert (NBM or Ch4) are major cholinergic nuclei of the human basal forebrain, a complex that is affected in Alzheimer's disease (AD). Sex hormones influence the function of these cholinergic neurons in animals and humans and we showed earlier that estrogen and androgen receptors (AR) are present in both the VDB and the NBM of young patients of 20-39 years of age. The aim of the present study was to investigate whether AR expression changes in relation to aging and AD. In both brain areas of male and female patients over the age of 56 nuclear staining had almost disappeared and cytoplasmic AR expression was decreased. This decrease was most pronounced in the VDB of men. In addition, the proportion of neurons showing cytoplasmic AR expression was higher in control aged women than in control aged men in both the VDB and the NBM. Surprisingly, cytoplasmic ARs were significantly decreased in the VDB and the NBM only in AD women and not in AD men. These observations suggest the possible involvement of androgens in the functional changes of the basal forebrain nuclei in aging and AD.
布罗卡斜角带垂直支(VDB或Ch2)和迈内特基底核(NBM或Ch4)是人类基底前脑的主要胆碱能核团,该复合体在阿尔茨海默病(AD)中会受到影响。性激素会影响动物和人类中这些胆碱能神经元的功能,我们之前发现,雌激素和雄激素受体(AR)存在于20至39岁年轻患者的VDB和NBM中。本研究的目的是调查AR表达是否会随衰老和AD而发生变化。在56岁以上男性和女性患者的两个脑区中,细胞核染色几乎消失,细胞质AR表达降低。这种降低在男性的VDB中最为明显。此外,在VDB和NBM中,显示细胞质AR表达的神经元比例在老年对照女性中高于老年对照男性。令人惊讶的是,仅在AD女性的VDB和NBM中,细胞质AR显著降低,而在AD男性中则没有。这些观察结果表明,雄激素可能参与了衰老和AD过程中基底前脑核团的功能变化。