Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice
Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice
复制标题
DOI：
10.1016/j.brainres.2006.04.109
复制
发表时间：
2006-07-12
期刊：
影响因子：
2.9
通讯作者：
Gaertner, Ulrich
中科院分区：
文献类型：
--
作者：
Alpar, Aldn;Ueberham, Uwe;Gaertner, Ulrich
淀粉样蛋白- β肽（A β）在脑实质细胞外沉积是阿尔茨海默病的特征之一，被认为可诱导神经元细胞体、轴突和树突的反应性和退行性改变。特别是，在淀粉样斑块内部和附近，观察到明显的形态学改变，包括神经突轨迹的改变、树突直径和脊柱密度的减少。除了这些斑块相关的焦像差外，关于全局树突形态的改变，包括顶端和基部乔木的详细和比较定量分析，我们所知甚少。本研究的目的是研究淀粉样斑块沉积和可溶性A β升高对突变型人淀粉样前体蛋白（hAPP）转基因小鼠(系Tg2576；杨凤英，杨凤英，杨凤英，杨凤英，杨凤英，杨凤英，转基因小鼠的相关记忆缺陷、β - β蛋白升高和淀粉样蛋白斑块的研究，科学进展（1996）：99-102。对初生体感觉皮层逆行标记胼胝体突起锥体细胞进行三维分析。虽然基部树突未受影响，但顶端树的分析揭示了一些明确的形态变化。因此，TG2576小鼠的根茎总长度缩短，分支减少。近端树突节段直径增大，远端树突节段直径减小。对基树和根尖树的脊柱数量和分布的分析表明，沿树突整个过程的脊柱密度显著减少。研究结果表明，A β相关病理在不同程度上诱导了基底和根尖乔木的形态畸变，而这些畸变与斑块相关的直接变化无关。(c) 2006 Elsevier B.V.版权所有
The extracellular deposition of amyloid-beta peptide (A beta) in brain parenchyma is one of the characteristic features of Alzheimer's disease and is suggested to induce reactive and degenerative changes in neuronal cell bodies, axons and dendritic processes. In particular, within and in close proximity to amyloid plaques, distinctive morphological alterations have been observed, including changes in neurite trajectory and decreases in dendritic diameter and in spine density. Apart from these plaque-associated focal aberrations, little is known regarding modifications of the global dendritic morphology including the detailed and comparative quantitative analysis of apical and basal arbors. The objective of the present study was to investigate the effects of amyloid plaque deposition and elevated soluble A beta on neuronal morphology in mutant human amyloid precursor protein (hAPP) transgenic mice (line Tg2576; [K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, G. Cole, Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice, Science 274 (1996) 99-102]). Retrogradelly labeled callosal-projecting pyramidal cells in the primary somatosensory cortex were three-dimensionally analyzed. Although basal dendrites remained unaffected, analysis of apical trees revealed a number of unambiguous morphological changes. Thus, in TG2576 mice, the apical arbors were shortened in total length and less branched. Furthermore, the diameter of proximal dendritic segments was increased whereas that of distal segments was reduced. Analysis of spine numbers and distribution on basal and apical trees demonstrated a significant reduction in spine densities along the whole course of dendrites. The findings suggest that A beta-related pathology induces morphological aberrations in basal and apical arbors to different degrees which are unrelated to direct plaque-associated changes. (c) 2006 Elsevier B.V. All rights reserved.