Evidence for normal aging of the septo-hippocampal cholinergic system in apoE (-/-) mice but impaired clearance of axonal degeneration products following injury
Evidence for normal aging of the septo-hippocampal cholinergic system in apoE (-/-) mice but impaired clearance of axonal degeneration products following injury
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DOI：
10.1006/exnr.1998.6818
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发表时间：
1998-06-01
影响因子：
5.3
通讯作者：
Holtzman, DM
中科院分区：
文献类型：
--
作者：
Fagan, AM;Murphy, BA;Holtzman, DM
apoE基因的104等位基因与阿尔茨海默病（AD）风险增加和某些急性脑损伤后临床预后不良的相关性引发了对apoE神经生物学的兴趣。ApoE（-/-）小鼠为研究apoE在体内神经系统中的作用提供了工具。由于AD患者基底前脑胆碱能系统的完整性受到严重损害，功能障碍的严重程度与apoE 4基因剂量相关，本研究验证了apoE是维持基底前脑胆碱能神经元（BFCN）正常完整性所必需的假设。对apoE（-/-）小鼠衰老过程中和损伤后隔-海马胆碱能系统进行组织学和生化分析。使用无偏定量方法，通过内侧隔中的p75（NTR）免疫反应神经元数量和大小、海马中的胆碱能纤维密度以及海马、皮质、和纹状体的变化。此外，在apoE（-/-）小鼠中，穹窿海马伞横断后胆碱能神经元的存活率和大小与对照组没有差异。而apoE（-/-）小鼠内嗅皮层损伤后，在去传入海马区仍有变性产物存在。这些数据表明，虽然apoE是不需要的BFCN在体内的维护，它可能发挥作用，在清除胆固醇负载的神经变性产品脑损伤后。(C)北京：科学出版社.
The association of the epsilon 4 allele of apoE with increased risk for Alzheimer's disease (AD) and with poor clinical outcome after certain acute brain injuries has sparked interest in the neurobiology of apoE. ApoE (-/-) mice provide a tool to investigate the role of apoE in the nervous system in vivo. Since integrity of the basal forebrain cholinergic system is severely compromised in AD, with severity of dysfunction correlating with apoE4 gene dosage, the present study tested the hypothesis that apoE is required to maintain the normal integrity of basal forebrain cholinergic neurons (BFCNs). Histological and biochemical analyses of the septo-hippocampal cholinergic system were performed in apoE (-/-) mice during aging and following injury. Using unbiased quantitative methods, there was little or no evidence for defects in the septo-hippocampal cholinergic system, as assessed by p75(NTR)-immunoreactive neuron number and size in the medial septum, cholinergic fiber density in the hippocampus, and choline acetyltransferase activity in the hippocampus, cortex, and striatum in aged apoE (-/-) mice (up to 24 months of age) as compared to age-matched wild-type mice of the same strain. In addition, cholinergic neuronal survival and size following fimbria-fornix transection in apoE (-/-) mice did not differ from controls. However, following entorhinal cortex lesion, there was persistence of degeneration products in the deafferented hippocampus in apoE (-/-) mice. These data suggest that although apoE is not required for the maintenance of BFCNs in vivo, it may play a role in the clearance of cholesterol-laden neurodegeneration products following brain injury. (C) 1998 Academic Press.