生理運動可以透過增加腦源神經生長因子(BDNF)進而促進動物學習及記憶功能。已知強制性跑步機運動及自主性滾輪運動對小鼠在莫氏水迷宮(Morris water maze)及被動避險(passive avoidance)學習與記憶表現上產生不同影響。兩種運動皆能促進小鼠在莫氏水迷宮測試上之學習與記憶表現，然而只有強制性跑步機運動能改善小鼠之被動避險學習與記憶，此乃因前者提升了杏仁核BDNF及突觸標的融合蛋白(synaptotagmin I)之表現。據此，設立研究假說，即不同運動模式藉由影響不同腦區神經可塑性蛋白質表現，進而影響不同形式學習記憶之表現，而此現象亦應可在它種動物得到印証。為證實此假說，我們使用兩種不同運動方式訓練大鼠，並以兩種相近的學習記憶法（海馬迴依賴型環境恐懼制約contextual fear conditioning及杏仁核依賴型線索恐懼制約cued fear conditioning）測試其學習與記憶表現之異同。Sprague-Dawley大鼠隨機分成強制性跑步機運動、自主性滾輪運動及無運動組別，在四週訓練結束後，接受海馬迴依賴型環境恐懼制約及杏仁核依賴型線索恐懼制約的學習記憶測試，或直接犧牲檢驗相關腦區中BDNF受體TrkB、synaptotagmin I、synaptotagmin IV及SNAP-25蛋白之表現以及神經細胞之型態。研究結果顯示：1)兩種運動皆能提昇大鼠對環境恐懼制約學習能力; 2)然只有強制性跑步機運動能促進大鼠對線索恐懼制約學習能力; 3)兩種運動皆能促進海馬迴TrkB及SNAP-25蛋白分子之表現，但只有強制性跑步機運動能提升動物杏仁核TrkB及SNAP-25蛋白分子之表現; 4)不論強制性跑步機運動或自主性滾輪運動對大鼠腦中臨邊系統(brain limbic tissues) 之synaptotagmin I及synaptotagmin IV蛋白表現皆無顯著影響; 5)在相關腦區中給予TrkB抑制劑K252a皆會抑制運動所促進之對應恐懼制約的學習能力; 6)強制性跑步機運動能提升大鼠杏仁核側底核神經錐狀細胞樹突之生長; 7)兩種運動對大鼠海馬迴之齒狀回顆粒細胞樹突之生長並無顯著性影響。因此，強制性跑步機運動或自主性滾輪運動對動物不同形式之學習記憶能產生不同之影響，可肇因於兩種不同運動模式能對動物海馬迴及杏仁核突觸可塑性相關蛋白質表現及相關腦區內神經的型態產生不同之影響。

Exercise increases the level of brain-derived neurotrophic factor (BDNF) and enhances learning and memory. Studies from our laboratory have demonstrated that chronic treadmill and wheel running differentially affect the mouse’s performance in Morris water maze and passive avoidance. Both exercise paradigms improve the former task, while only treadmill running improves the latter. Moreover, the treadmill running-improved passive avoidance performance requires the upregulation of amygdalar BDNF signaling pathway and synaptotagmin I (Syt I) expression. Therefore, the differential effects of two exercise paradigms on different forms of learning and memory are likely due to the exercise-induced adaptations in different brain regions. Whether this hypothesis holds true in other animal models of learning and memory remains to be verified. In this study, we investigated the effects of treadmill and wheel running in rats on two closely related learning and memory tasks, i.e., the hippocampus-dependent contextual fear conditioning and amygdala-dependent cued fear conditioning. Sprague-Dawley rats were randomly assigned to treadmill, wheel running, or sedentary groups. At the end of 4-wk training period, rats either received two fear conditioning tests or were sacrificed for brain regional examinations of neuroplasticity-related molecules (TrkB, Syt I, Syt IV and SNAP-25) and local neuron morphology. Our results indicated that 1) both forms of exercise elevated contextual fear learning; 2) treadmill running, but not wheel running, facilitated cued fear learning; 3) both forms of exercise increased hippocampal TrkB and SNAP-25 levels, but only treadmill significantly increased amygdalar TrkB and SNAP-25 levels; 4) neither forms of exercise significantly affected the expression of Syt I and Syt IV in the brain limbic tissues; 5) local injection of K252a ( a TrkB kinase inhibitor) into hippocampus or amygdala abolished the exercise-facilitated contextual or cued fear learning performance; 6) treadmill running increased the number of dendritic branches and total dendritic length of pyramidal cells in the basolateral amygdala; 7) neither forms of exercise significantly affected the morphology of granule cells in the hippocampal dentate gyrus. Taken together, different exercise paradigms exerted differential effects on hippocampus-dependent and amygdala-dependent learning due to diverse impacts on the synaptic plasticity-related proteins expression in the hippocampus and amygdala. Moreover, such effects might be accompanied with local changes in neuronal morphology.

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