Department of Anatomy and Cell Biology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea.
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
Mol Med Rep. 2018 May;17(5):6465-6471. doi: 10.3892/mmr.2018.8705. Epub 2018 Mar 8.
Glutamate is a major excitatory neurotransmitter that is stored in vesicles located in the presynaptic terminal. Glutamate is transported into vesicles via the vesicular glutamate transporter (VGLUT). In the present study, the age‑associated changes of the major VGLUTs, VGLUT1 and VGLUT2, in the hippocampus were investigated, based on immunohistochemistry and western blot analysis at postnatal month 1 (PM1; adolescent), PM6, PM12 (adult group), PM18 and PM24 (the aged groups). VGLUT1 immunoreactivity was primarily detected in the mossy fibers, Schaffer collaterals and stratum lacunosum‑moleculare. By contrast, VGLUT2 immunoreactivity was observed in the granule cell layer and the outer molecular layer of the dentate gyrus, stratum pyramidale, Schaffer collaterals and stratum lacunosum‑moleculare in the hippocampal CA1‑3 regions. VGLUT1 immunoreactivity and protein levels remained constant across all age groups. However, VGLUT2 immunoreactivity and protein levels decreased in the PM3 group when compared with the PM1 group. VGLUT2 immunoreactivity and protein levels were not altered in the PM12 group; however, they increased in the PM18 group. In addition, in the PM18 group, highly immunoreactive VGLUT2 cells were also identified in the stratum radiatum and oriens of the hippocampal CA1 region. In the PM24 group, VGLUT2 immunoreactivity and protein levels were significantly decreased and were the lowest levels observed amongst the different groups. These results suggested that VGLUT1 may be less susceptible to the aging process; however, the increase of VGLUT2 in the non‑pyramidal cells in the PM18 group, and the consequent decrease in VGLUT2, may be closely linked to age‑associated memory impairment in the hippocampus.
谷氨酸是一种主要的兴奋性神经递质，储存在位于突触前末梢的小泡中。谷氨酸通过囊泡谷氨酸转运体（VGLUT）被转运到小泡中。在本研究中，通过免疫组织化学和 Western blot 分析，研究了海马中主要 VGLUT 即 VGLUT1 和 VGLUT2 在出生后第 1 个月（青少年）、第 6 个月、第 12 个月（成年组）、第 18 个月和第 24 个月（老年组）的年龄相关性变化。VGLUT1 免疫反应主要在苔藓纤维、Schaffer 侧支和腔隙分子层中检测到。相比之下，VGLUT2 免疫反应在颗粒细胞层和齿状回的外分子层、海马 CA1-3 区的锥体层、Schaffer 侧支和腔隙分子层中观察到。VGLUT1 免疫反应和蛋白水平在所有年龄组中均保持不变。然而，与 PM1 组相比，PM3 组的 VGLUT2 免疫反应和蛋白水平降低。在 PM12 组中，VGLUT2 免疫反应和蛋白水平没有改变；然而，在 PM18 组中增加。此外，在 PM18 组中，海马 CA1 区的放射层和始层中也鉴定出高度免疫反应性的 VGLUT2 细胞。在 PM24 组中，VGLUT2 免疫反应和蛋白水平显著降低，是不同组中最低的水平。这些结果表明，VGLUT1 可能对衰老过程的敏感性较低；然而，在 PM18 组中，非锥体细胞中 VGLUT2 的增加，以及随后 VGLUT2 的减少，可能与海马中与年龄相关的记忆损伤密切相关。
