Modification upon aging of the density of presynaptic modulation systems in the hippocampus
Modification upon aging of the density of presynaptic modulation systems in the hippocampus
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DOI：
10.1016/j.neurobiolaging.2008.01.003
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发表时间：
2009-11-01
影响因子：
4.2
通讯作者：
Cunha, Rodrigo A.
中科院分区：
文献类型：
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作者：
Canas, Paula M.;Duarte, Joao M. N.;Cunha, Rodrigo A.
不同的突触前神经调节系统已被探索作为可能的目标，以管理神经退行性疾病。然而，大多数研究使用年轻的成年动物，而神经退行性疾病在老年人中普遍存在。因此，我们现在通过Western印迹分析探索不同突触前标记物和受体的密度如何随着大鼠海马突触体（纯化的神经末梢）的老化而变化。与2月龄大鼠的突触体膜相比，突触前蛋白（突触素或SNAP-25）的密度在18-24个月时降低。与此同时，谷氨酸能终末标记物（vGluT 1或vGluT 2）和胆碱能终末标记物（vAChT）从12至18个月开始随着年龄的增长不断下降，而GABA能（vGAT）的密度仅在24个月后下降。抑制性A I和CB 1受体密度随着年龄的增长而下降，而易化性mGluR 5和P2 Y1受体密度大致恒定，易化性A（2A）受体密度在18-24个月时增加。因此，衰老导致兴奋性与抑制性神经末梢标记物的不平衡，并导致抑制性而非易化性突触前调制系统的显著减少。(C)2008年爱思唯尔公司All rights reserved.
Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve terminals). Compared to synaptosomal membranes from 2-month-old rats, the density of presynaptic proteins (synaptophysin or SNAP-25) decreased at 18-24 months. In parallel, markers of glutamatergic terminals (vGluT1 or vGluT2) and cholinergic terminal markers (vAChT) constantly decreased with aging from 12 to 18 months onwards, whereas the densities of GABAergic (vGAT) only decreased after 24 months. Inhibitory A I and CB, receptor density tended to decrease with aging, whereas facilitatory mGluR5 and P2Y1 receptor density was roughly constant and facilitatory A(2A) receptor density increased at 18-24 months. Thus aging causes an imbalance of excitatory versus inhibitory nerve terminal markers and causes a predominant decrease of inhibitory rather than facilitatory, presynaptic modulation systems. (C) 2008 Elsevier Inc. All rights reserved.