Mufson Elliott J, Ginsberg Stephen D, Ikonomovic Milos D, DeKosky Steven T
Department of Neurological Sciences and Alzheimer's Disease Center, Rush Presbyterian-St. Luke's Medical Center, Tech 2000, 2242 West Harrison St., Suite 200, Chicago, IL 60612, USA.
J Chem Neuroanat. 2003 Dec;26(4):233-42. doi: 10.1016/s0891-0618(03)00068-1.
The human cholinergic basal forebrain (CBF) is comprised of magnocellular hyperchromic neurons within the septal/diagonal band complex and nucleus basalis (NB) of Meynert. CBF neurons provide the major cholinergic innervation to the hippocampus, amygdala and neocortex. They play a role in cognition and attentional behaviors, and are dysfunctional in Alzheimer's disease (AD). The human CBF displays a continuum of large cells that contain various cholinergic markers, nerve growth factor (NGF) and its cognate receptors, calbindin, glutamate receptors, and the estrogen receptors, ERalpha and ERbeta. Admixed with these cholinergic neuronal phenotypes are smaller interneurons containing the m2 muscarinic acetylcholine receptor (mAChRs), NADPH-diaphorase, GABA, calcium binding proteins and several inhibitory neuropeptides including galanin (GAL), which is over expressed in AD. Studies using human autopsy material indicate an age-related dissociation of calbindin and the glutamate receptor GluR2 within CBF neurons, suggesting that these molecules act synergistically to induce excitotoxic cell death during aging, and possibly during AD. Choline acetyltrasnferease (ChAT) activity and CBF neuron number is preserved in the cholinergic basocortical system and up regulated in the septohippocampal system during prodromal as compared with end stage AD. In contrast, the number of CBF neurons containing NGF receptors is reduced early in the disease process suggesting a phenotypic silence and not a frank loss of neurons. In end stage AD, there is a selective reduction in trkA mRNA but not p75(NTR) in single CBF cells suggesting a neurotrophic defect throughout the progression of AD. These observations indicate the complexity of the chemoanatomy of the human CBF and suggest that multiple factors play different roles in its dysfunction in aging and AD.
人类胆碱能基底前脑（CBF）由隔区/斜角带复合体和迈内特基底核（NB）内的大细胞性深染神经元组成。CBF神经元为海马体、杏仁核和新皮质提供主要的胆碱能神经支配。它们在认知和注意力行为中发挥作用，并且在阿尔茨海默病（AD）中功能失调。人类CBF呈现出一系列大细胞，这些细胞含有各种胆碱能标志物、神经生长因子（NGF）及其同源受体、钙结合蛋白、谷氨酸受体以及雌激素受体ERα和ERβ。与这些胆碱能神经元表型混合存在的是较小的中间神经元，它们含有m2毒蕈碱型乙酰胆碱受体（mAChRs）、NADPH - 黄递酶、γ - 氨基丁酸、钙结合蛋白以及几种抑制性神经肽，包括在AD中过度表达的甘丙肽（GAL）。使用人类尸检材料的研究表明，CBF神经元内钙结合蛋白和谷氨酸受体GluR2存在与年龄相关的解离，这表明这些分子在衰老过程中，可能也在AD过程中协同作用诱导兴奋性毒性细胞死亡。与AD终末期相比，在疾病前驱期，胆碱能基底皮质系统中胆碱乙酰转移酶（ChAT）活性和CBF神经元数量得以保留，而在隔海马系统中则上调。相反，在疾病过程早期，含有NGF受体的CBF神经元数量减少，这表明是表型沉默而非神经元的明显丧失。在AD终末期，单个CBF细胞中trkA mRNA有选择性减少，但p75（NTR）没有减少，这表明在AD进展过程中存在神经营养缺陷。这些观察结果表明人类CBF化学解剖结构的复杂性，并提示多种因素在其衰老和AD功能障碍中发挥不同作用。
