幼年小鼠給予C16神經醯胺對於其成鼠後行為與記憶之影響

Abstract

神經醯胺為一種重要的細胞結構，參與許多細胞活動，在自然界中多以長碳鏈之形式存在。有研究指出小鼠攝取高油脂飲食會造成體內神經醯胺濃度增加，並使得體內葡萄糖濃度受到影響，而產生胰島素拮抗現象。研究也發現，許多代謝相關疾病，如：第二型糖尿病、肥胖等，均會增加病人認知受損的風險，相反的，若是施予認知受損病人胰島素增敏劑，可改善認知受損情況，不過在認知損傷與胰島素拮抗之間之關係還需要更深入之探討。目前並沒有研究針對神經醯胺對於幼鼠成長過程之生理及行為影響作探討。所以本實驗以三週大的小鼠於皮下注射C16神經醯胺，模擬可能因飲食所導致的堆積，也以高脂飲食誘導小鼠發生肥胖，檢測神經醯胺的影響。結果顯示，C16神經醯胺對於小鼠體重及血糖，或在餵食高油脂飲食後的體重及血糖等，皆沒有顯著的影響。在動物行為的結果發現，肥胖會大幅降低小鼠的自發探索能力。注射C16神經醯胺之小鼠，在莫氏水迷津實驗中，不論是攝食何種飼料的小鼠，其短期、長期記憶測驗皆有顯著地提升。進一步研究發現經過C16神經醯胺及油酸處理過的小鼠初級神經細胞，與記憶相關之蛋白CaMK II T286之磷酸化量會上升。綜合以上，幼年給予C16神經醯胺之小鼠，於成鼠時其記憶行為似乎有增進的現象，其機制有待進一步探討，但由體外實驗顯示可能與增進CaMK II磷酸化有關。

Ceramide is an important membrane structure involving many different functions in the cell. It naturally occurrs 16 to 24 carbons in length. There are reports indicate that mice fed with high fat diet can cause ceramide accumulation, leading to insulin resistance. In addition, many metabolic diseases such as type 2 diabetes and obesity might increase the risk of developing mild cognitive impairment. In contrast, treatment with insulin-sensitizing agents could improve the cognitive performance. Thus far, there is no evidence demonstrating the relationship between cognitive impairment and insulin resistance. Likewise, there is no report regarding the effect of ceramide given at childhood on adult memory behavior. Three-weeks old mice were injected with C16 ceramide or mineral oil for a month. These mice were further fed with normal chow or high fat diet. The results show that there are no significant differences on mice’s body weight and blood glucose between C16 ceramide treatment and control. Obesity caused by high fat diet significant affects the locomotor activity of mice. Interestingly, C16 ceramide could promote the short-term and long-term memory in ether diet these mice were given. Furthermore, p-CaMK II T286 was increased in the primary neurons treated with C16 ceramide in vitro. Taken together, C16 ceramide given at childhood could enhance the memory behavior at adult mice. It is possible to link to the change of CaMK II activity. The detail molecular mechanism remains to be investigated.