A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic basal forebrain neurons in Alzheimer's disease
A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic basal forebrain neurons in Alzheimer's disease
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DOI：
10.1111/j.1750-3639.1997.tb01058.x
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发表时间：
1997-04-01
期刊：
影响因子：
6.4
通讯作者：
Mufson, EJ
中科院分区：
文献类型：
--
作者：
Bowser, R;Kordower, JH;Mufson, EJ
含甘丙肽（GAL）的肽纤维系统支配基底前脑，并已被证明在阿尔茨海默病（AD）中过度支配剩余的胆碱能神经元。GAL调节乙酰胆碱的释放，因此，可能会抑制这种神经递质在存活的胆碱能基底前脑（CBF）神经元在AD。本研究的目的是确定假定的GAL免疫反应过程和CBF神经元之间的突触接触，并评估这些过程是否在AD患者肥大。我们通过共聚焦激光显微镜观察了AD和帕金森病并发AD（PD/AD）患者中含GAL纤维的高神经支配。甘丙肽能纤维常直接贴附于残存的CBF神经元和胆碱能细胞索马和树突上。我们的研究结果表明，含GAL的纤维是在正常年龄的人直接贴壁CBF神经元，这种表型增强AD和PD/AD，表明直接突触接触之间发生的含GAL的纤维和CBF神经元。由于GAL可以调节胆碱能神经元的乙酰胆碱释放，因此AD和PD/AD患者中GAL纤维的过度神经支配可能进一步减少剩余CBF神经元的乙酰胆碱释放。我们认为，单纯基于乙酰胆碱酯酶抑制剂的治疗可能不足以有效地增加皮质乙酰胆碱水平。
The galanin (GAL) containing peptide fiber system innervates the basal forebrain and has been shown to hyperinnervate remaining cholinergic neurons in Alzheimer's disease (AD). GAL modulates the release of acetylcholine and, therefore, may depress this neurotransmitter in surviving cholinergic basal forebrain (CBF) neurons in AD. The aim of this study was to identify putative synaptic contacts between GAL immunoreactive processes and CBF neurons and evaluate whether these processes hypertrophy in AD patients. We observed by confocal laser microscopy a hyperinnervation of GAL-containing fibers in both AD and Parkinson's disease patients with concurrent AD (PD/AD). Galaninergic fibers were often seen in direct apposition to remaining CBF neurons and enwrapped cholinergic cell soma and dendrites. Our results demonstrate that GAL-containing fibers are in direct apposition to CBF neurons in normal-aged humans and that this phenotype is enhanced in AD and PD/AD, suggesting that direct synaptic contacts occur between GAL-containing fibers and CBF neurons. Because GAL can modulate acetylcholine release from cholinergic neurons, hyperinnervation of GAL fibers in AD and PD/AD patients may further decrease release of acetylcholine from remaining CBF neurons. We propose that therapies based solely on acetylcholinesterase inhibitors may be insufficient to effectively increase cortical levels of acetylcholine.