卡路里節制改變小鼠海馬迴神經細胞結構並促進空間記憶

Abstract

卡路里節制在多種實驗動物模型的研究上發現能延長壽命，也能有效減少發生老化相關疾患發生的可能性，除此之外，亦能提升老鼠及人類的認知功能。為探討卡路里節制作用於記憶功能的機制，本實驗選擇空間記憶做分析，以Y型迷津作為空間記憶的測驗裝置，利用老鼠天生傾向探索新事物的特性，調整間隔時間以檢測卡路里節制對長期（間隔24小時）及短期（間隔2 小時）的空間記憶能力的影響。實驗結果發現，卡路里節制及正常飲食的小鼠在短期空間記憶表現並無差異，而隨間隔時間增長，一般飲食組小鼠的表現變差，相較之下卡路里節制小鼠的長期空間記憶則顯著表現較好。 記憶的改變可能來自大腦結構的改變，為探討卡路里節制影響認知功能的機制，本實驗著重形象學的分析，重新架構與空間記憶相關腦區——海馬迴中齒狀迴及CA1的神經細胞，結果發現卡路里節制減少樹突分叉數量及長度，另外樹突上與訊息傳遞、認知功能相關的突觸脊，其密度在卡路里節制下具有上升的現象。由上述結果可知，神經細胞樹突結構受到飲食操弄影響，進一步使用甲酚紫染色分析海馬迴神經細胞的分佈密度，不論在CA1、CA3或齒狀迴，卡路里節制組及正常飲食組間並無顯著差異；另外特別針對抑制型的GABA神經細胞分析，則發現在齒狀迴區域卡路里節制會使得GABA神經細胞數量顯著高於正常飲食組，CA1和CA3則無差異。此神經結構的改變以及抑制型神經細胞密度變化的結果可能提供了卡路里節制改善空間記憶的機制的新解釋。

Calorie restriction (CR) has been shown to extend lifespan and reduce the incidence and onset of aging-related disease in several animal models. It can also promote cognitive functions in mice and human. Among several type of memory, the spatial memory is analyzed in this study. Y-maze is chose as task to discuss the effect of CR on short-term (2 hours) and long-term (24 hours) spatial recognition memory. It is based on the natural tendency of mice to explore novelty that prevents emotional factors from influencing the result. I found that there is no difference between CR and AL mice in short-term memory task, however, CR mice has significantly better spatial recognition memory in long-term task. Since memory formation is generally associated with molecular and structural alterations, the dendritic structures of granule cells and pyramidal cells in dentate gyrus (DG) and CA1 regions of hippocampus are reconstructed to discuss how CR regulates brain functions. By using Golgi-Cox impregnation and Sholl analysis, we found that the number of intersections and the length of dendrites are significantly decreased in CR mice. On the other hand, the spine density is much higher in CR mice. Accordingly, the dendritic structure of CR mice is shrink and simpler compared to AL mice, while the function of neural cells may be elevated. In the following steps, the neural cell density in hippocampus is measured with Cresyl violet staining. The result shows that CR has no effect on total neural cell density. However, GABAergic neuron density is altered in DG but not in CA1 and CA3. These morphological findings may provide new explanation of the CR mechanism on spatial memory enhancement.