老化是中樞神經系統退化性疾病的主要危險因子之一。在年老的人類身上可以觀察到大腦皮質 (Cortex) 和海馬迴 (Hippocampus) 都有萎縮的情況；而隨著年齡的增長，人在學習和記憶能力上也皆有衰退的現象，而這些現象同樣在囓齒類動物身上可以觀察到。根據文獻報導指出，年老的囓齒類動物學習新事物的能力會降低，並且其大腦皮質以及海馬迴中突觸 (Synapses) 的數目、強度和可塑性都有減少的情形。跑步運動已知可改善認知能力與神經可塑性，但目前仍不清楚老化所引起的認知缺失是否可經由運動來改善。因此，本研究是要探討在不同年齡之小鼠經過跑步機訓練(Treadmill Running , TR) 之後，其學習和記憶能力的變化；並觀察小鼠腦中海馬迴CA3區錐狀神經細胞 (Hippocampus CA3 pyramidal neurons) 是否因運動而產生型態上或生物化學上的改變。實驗結果顯示，六週的跑步運動能有效地改善中年以及老年小鼠的空間學習與記憶能力，但在年輕小鼠上則無顯著性的變化。跑步運動之後，小鼠腦中海馬迴CA3區錐狀神經元的樹突分支 (dendrite branches) 、數目、樹突總長度 (dendrite lengths) 以及突觸小刺的密度都有顯著性的增加。另外，我們也經由西方墨點法發現突觸相關蛋白, SNAP25和SYT1，在中年期小鼠經過跑步運動之後可增加其蛋白的表現量。總和以上結果證實，跑步運動可增加中年期的小鼠腦中海馬迴CA3區神經元的突觸可塑性，進而增加神經細胞之間的溝通，而提升空間學習與記憶能力。因此，我們推測中年在老化的過程中扮演著一個關鍵的時刻；並且如果在中年的時候給予適當的運動，可能可以減緩老化的情形。

Aging implies a primary risk factor for disease of the central nervous system most especially neurodegenerative disorders. In aged humans the cortex and hippocampus atrophy and learning and reference memory declines. Similarly, the ability to learn new tasks decreases with age in rodents. The number of synaptic contacts, synaptic strength and plasticity are also reduced in the cortex and hippocampus of aged rodents. Although the aging-induced cognitive decline remains unclear, physical exercise has been shown to improve spatial learning and memory in humans and animals. Our results showed that six weeks of TR could improve spatial learning in middle and aged mice, but not in young mice. Moreover, TR also significantly enhanced memory performance in middle-aged mice, while the young and aged mice were unaffected by TR. At middle-aged mice, TR not only enhanced the dendritic branches and arbors but also increased the dendritic length and spine density of hippocampal CA3 pyramidal neurons. Furthermore, six weeks of TR induced the level of presynaptic proteins SNAP25 and SYT1 expression. These results suggest that enhancing learning and memory performance in middle-aged animals may be via the increases of synaptic vesicle in the hippocampus CA3 neurons.

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