Canas Paula M, Duarte João M N, Rodrigues Ricardo J, Köfalvi Attila, Cunha Rodrigo A
Centre for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal.
Neurobiol Aging. 2009 Nov;30(11):1877-84. doi: 10.1016/j.neurobiolaging.2008.01.003. Epub 2008 Mar 4.
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(1) and CB(1) 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.
不同的突触前神经调节系统已被探索作为治疗神经退行性疾病的可能靶点。然而，大多数研究使用的是年轻成年动物，而神经退行性疾病在老年人中更为普遍。因此，我们现在通过蛋白质印迹分析来探究在大鼠海马突触体（纯化的神经末梢）中，不同突触前标志物和受体的密度如何随衰老而变化。与2个月大的大鼠的突触体膜相比，18 - 24个月大时突触前蛋白（突触素或SNAP - 25）的密度降低。同时，从12到18个月起，谷氨酸能末梢标志物（vGluT1或vGluT2）和胆碱能末梢标志物（vAChT）随着衰老持续降低，而GABA能（vGAT）的密度仅在24个月后降低。抑制性A(1)和CB(1)受体密度倾向于随衰老而降低，而促进性的mGluR5和P2Y1受体密度大致保持恒定，促进性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志物失衡，并导致抑制性而非促进性突触前调节系统的显著减少。
