許多突觸蛋白及神經生長因子常參與在大腦邊緣系統的學習與記憶當中，例如Ca2+-dependent突觸蛋白synaptotagmin (Syt)及大腦衍生性神經生長因子(BDNF)和其受體TrkB皆參與在海馬迴或杏仁核相關之學習與記憶中。已知不論是非自主性跑步機運動或自主性滾輪運動皆能增進實驗動物的嫌惡學習與記憶(aversive learning and memory)或空間學習與記憶(spatial learning and memory)。然而，跑步機運動訓練是否透過增加上述分子之表現而達到促進學習與記憶的效果，以及不同的運動模式是否會對上述分子表現產生不同的影響進而調控不同的學習與記憶模式，目前則尚不清楚。為了回答這些問題，我們給予雄性BALB/c小鼠為期四週的跑步機運動訓練或自主性滾輪運動。運動後則以單次抑制性迴避學習(one-trial passive avoidance)或莫氏水迷宮(Morris water maze)測試其兩種學習與記憶之功能。另以酵素免疫分析法(ELISA)及西方點墨法(Western blotting)偵測小鼠大腦海馬迴及杏仁核區域之BDNF, TrkB和Syt I蛋白質表現。結果顯示: 1) 跑步機運動訓練及自主性滾輪運動皆能促進莫氏水迷宮之空間學習，但只有跑步機運動訓練能夠增進抑制性迴避之嫌惡學習與記憶; 2) 兩種運動模式皆能短暫增加海馬迴BDNF及持續增加海馬迴TrkB及Syt I蛋白質表現; 3) 只有跑步機運動訓練能夠短暫增加杏仁核BDNF及持續增加杏仁核Syt I蛋白質表現; 4) 在海馬迴或側杏仁核區域給予TrkB抑制劑，K252a，皆會抑制跑步機運動所促進的嫌惡學習與記憶及相關蛋白質的表現; 5) 在側杏仁核區域給予Syt I lentiviral -shRNA去抑制Syt I的表現，亦能抑制由跑步機運動所促進的嫌惡學習與記憶。由上述結果我們得知: 跑步機運動訓練所提升之BDNF/TrkB及Syt I的表現是參與在跑步機運動所增進的嫌惡學習與記憶當中。此外，跑步機運動訓練及自主性滾輪運動對嫌惡學習與記憶所產生不同之影響，則可能肇因於其對杏仁核突觸可塑性相關蛋白質表現影響之不同。

Learning and memory usually involve various synaptic proteins and neurotrophic factors in the limbic system. Among these molecules, synaptic protein such as synaptotagmin (Syt), a Ca2+-dependent synaptic vesicle protein, the brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB) have been discovered to play some roles in hippocampus or amygdala associated learning and memory. Recent studies indicate that both treadmill exercise and voluntary wheel running can improve aversive memory and spatial memory in rodents. Whether treadmill exercise training can improve learning and memory by upregulating some of these molecules and whether different types of exercise affect different learning/memory behavior tasks, BDNF-TrkB signaling and Syt expression differentially remains unclear. To answer these questions, BALB/c mice were trained by treadmill exercise or voluntary wheel running for 4 weeks. The ability of learning and memory after exercise was evaluated by passive avoidance (PA) test and Morris water maze. Hippocampal or amygdalar TrkB and Syt I protein expression after exercise were determined by Western blotting and BDNF was evaluated by ELISA. Our results showed that 1) both treadmill exercise and wheel running improve spatial learning and memory in Morris water maze, but only treadmill exercise improves aversive memory in PA test; 2) Both two exercises transiently increased the hippocampal BDNF level and persistently increased the hippocampal protein levels of full-length TrkB and Syt; 3) Only treadmill exercise transiently increased the amygdalar BDNF level and persistently increased the amygdalar protein levels of Syt; 4) Local administration of K252a into the hippocampus or basolateral amygdala to blunt TrkB signaling abolished treadmill exercise-enhanced PA performance and related protein expression; 5) Local administration of Syt I lentiviral-shRNA into the basolateral amygdala to inhibit Syt I expression also abolished treadmill exercise-enhanced PA performance and amygdalar Syt I expression. In conclusion, these data suggest that the upregulation of TrkB and Syt I may contribute to the exercise-facilitated aversive memory. Furthermore, moderate treadmill exercise and voluntary wheel running have differential effects on the aversive learning and memory, possibly due to the diverse influences on synaptic plasticity-related proteins in the amygdala.

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