Yoo Dae Young, Jung Hyo Young, Kim Jong Whi, Yim Hee Sun, Kim Dae Won, Nam Hajin, Suh Jun Gyo, Choi Jung Hoon, Won Moo-Ho, Yoon Yeo Sung, Hwang In Koo
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 Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangneung‑Wonju National University, Gangneung, Gangwon 25457, Republic of Korea.
Mol Med Rep. 2016 Nov;14(5):4755-4760. doi: 10.3892/mmr.2016.5804. Epub 2016 Oct 5.
Dynamin 1 is a known synaptic protein, which has is key in the presynaptic regulation of endocytosis. The present study investigated the association between age and the observed changes in Morris water maze performance, and immunoreactivity and protein levels of dynamin 1 in the mouse hippocampal formation. In addition, the effects of dynasore, an inhibitor of dynamin 1, on the hippocampal dependent memory were determined to elucidate the correlation between dynamin 1 and memory. In the training phase of the Morris water maze task, the mean escape latency of the aged group (24 months old) was significantly longer, compared with that of the adult group (4 months old), although the average swimming speed and the total distance traveled during the probe trial were similar in the two groups. In the aged group, the time spent locating the target platform was significantly longer and the time spent in the correct quadrant was significantly shorter, compared with those in the adult group. In the adult group, a moderate level of dynamin 1 was detected in the hippocampal CA1 and CA3 regions, and in the dentate gyrus. In the aged group, the immunoreactivity of dynamin 1 was almost eliminated in the CA3 region and the dentate gyrus. In addition, the protein levels of dynamin 1 in the brain were significantly lower in the aged group, compared with those in the adult group. The direct infusion of dynasore, significantly reduced the contextual memory, compared with that of animals in the vehicle‑treated group. These results suggested that dynamin 1 was susceptible to the aging process, and that a reduction in dynamin 1 may result in hippocampal‑dependent memory deficits by disrupting endocytosis and the release of neurotransmitters.
发动蛋白1是一种已知的突触蛋白，在突触前内吞作用调节中起关键作用。本研究调查了年龄与观察到的小鼠在莫里斯水迷宫实验中的行为变化、海马结构中发动蛋白1的免疫反应性和蛋白质水平之间的关联。此外，还测定了发动蛋白1抑制剂dynasore对海马依赖性记忆的影响，以阐明发动蛋白1与记忆之间的相关性。在莫里斯水迷宫任务的训练阶段，老年组（24个月大）的平均逃避潜伏期明显长于成年组（4个月大），尽管在探索试验中两组的平均游泳速度和总游动距离相似。与成年组相比，老年组找到目标平台所用的时间明显更长，而在正确象限所花的时间明显更短。在成年组中，在海马CA1和CA3区域以及齿状回中检测到中等水平的发动蛋白1。在老年组中，发动蛋白1在CA3区域和齿状回中的免疫反应性几乎消失。此外，与成年组相比，老年组大脑中发动蛋白1的蛋白质水平明显更低。与接受载体处理的动物相比，直接注射dynasore显著降低了情境记忆。这些结果表明，发动蛋白1易受衰老过程的影响，发动蛋白1的减少可能通过破坏内吞作用和神经递质释放导致海马依赖性记忆缺陷。
