Department of Biology and Biotechnology - Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, University of Pavia , Via Ferrata, 9, 27100 Pavia, Italy.
J Proteome Res. 2013 Dec 6;12(12):5422-35. doi: 10.1021/pr400834g. Epub 2013 Nov 7.
The effect of aging on hippocampus is often confounded by diseases that commonly occur in the elderly. In this research, functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the hippocampus of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from glutamatergic mossy fiber endings connecting granule cells of dentate gyrus with apical dendrites of CA3 pyramidal cells, and the "small" synaptosomes, derived from the cholinergic small nerve endings of septo-hippocampal fibers, whose projections reach CA1 pyramidal cells, were isolated. Because most brain disorders are associated with bioenergetic changes, the maximum rate (V(max)) of selected enzymes of glycolysis, Krebs cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features coherently with the selective vulnerability of the respective hippocampal subfields to Alzheimer's disease and cerebral ischemia. This study represents a reliable model to study in vivo (i) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (ii) the responsiveness to noxious stimuli, and (iii) the effects of drugs, discriminating their action sites at subcellular level.
衰老对海马体的影响常常与老年人中常见的疾病混淆。在这项研究中，功能蛋白质组学被用于描述 Wistar 大鼠海马体中不同神经元通路能量代谢随年龄变化的情况，这些大鼠的年龄分别为 2、6、12、18 和 24 个月。“大”突触体来源于谷氨酸能苔藓纤维末梢，与齿状回颗粒细胞的顶树突相连；“小”突触体来源于隔海马纤维的胆碱能小神经末梢，其投射到达 CA1 锥体神经元。因为大多数脑部疾病都与生物能量变化有关，所以评估了糖酵解、三羧酸循环、谷氨酸和氨基酸代谢以及乙酰胆碱分解代谢的选定酶的最大速率（V(max)）。结果表明，“大”和“小”突触体具有特定的、独立的代谢特征，与各自海马区对阿尔茨海默病和脑缺血的选择性易损性一致。这项研究代表了一种可靠的模型，可用于研究依赖于能量代谢的一些脑部疾病的生理病理学分子机制、对有害刺激的反应以及药物的作用，能够在亚细胞水平上区分它们的作用部位。
