DWV感染與細胞外腺苷信號在西方蜜蜂的神經功能中作用關聯性之研究

Abstract

畸翅病毒 (Deformed Wing Virus, DWV) 普遍存在台灣的蜂群中，此病毒被認為與造成蜜蜂學習記憶能力衰退的蜂群衰竭失調症 (Colony Collapse Disorder, CCD)有極高的關聯性，並對台灣農業經濟產生危害。腺苷訊息傳遞是維持動物免疫與大腦記憶學習的重要途徑之一，而在昆蟲中，腺苷可經由調節醣類代謝，增強昆蟲免疫並抵抗病原菌，但對於昆蟲記憶學習能力的角色還尚待釐清。前人的研究指出，腺苷傳遞路徑所調控的醣類代謝會影響人腦中的記憶能力，但目前還不清楚對無脊椎動物的影響。此研究在於了解腺苷傳遞途徑在無脊椎動物腦中的作用機制。此外，藉此將可以幫助我們釐清蜜蜂蜂群如何受到病毒感染後使抑制腺苷傳導路徑使腦部能量受損，並且可以找到影響的相關記憶基因或是影響神經的分子途徑。我們實驗結果發現，蜜蜂學習記憶能力在感染DWV後顯著降低，蜜蜂身體的腺苷受體表現量上升，腦部腺苷受體表現量卻明顯下降，而且包含最終能量產物例如葡萄糖與三磷酸腺苷的濃度也在身體與腦中顯示出一致的差異性。顯示不僅腺苷訊息傳遞參與在DWV的致病途徑中，也因此造成腦與身體能量代謝出現失衡，使得腦部能量供應不足，因而讓ATP參與調控的Glu-Gln循環受到影響，最終導致長期記憶出現缺失。此外，我們也藉由餵食蜜蜂增加腦部腺苷路徑代謝效力，證明除了對受影響的記憶相關基因表現量有所回升，也發現在受感染蜜蜂中存活率與長期記憶表現都有正向恢復的現象。在學理研究方面，本研究可當作探究腺苷傳導路徑與腦部記憶學習能力關聯性之生物模型，有助於我們更進一步了解受感染動物能量調節與腦部神經功能異常之原因。

Apis mellifera, also known as the western honeybee, belongs to the order Hymenoptera and the family Apidae. In recent years, an increasing number of colonies worldwide have been affected by missing worker bees, a condition termed colony collapse disorder (CCD). This phenomenon may be caused by pathogens, pesticides, or even interactions between those two factors by creating stressful environments for honeybees. Honeybees are susceptible to infection by viruses that might cause colony diseases, such as deformed wing virus (DWV). DWV is present in 90% of hives and is the most common virus in Taiwan. DWV infection during the developmental cycle may result in deformed wings and newly emerged worker bees may suffer disabilities or even death, though there are no obvious symptoms when adult bees are infected by DWV. Previous studies have shown that bees infected with DWV display significant effect on learning ability and memory, but little is known about the mechanism of memory loss in honeybee during DWV infection. Adenosine signaling is one of important pathway regulating the brain and energy metabolism function in animals. In the insects, it was recently demonstrated that adenosine (Ado) signaling plays an important role controlling the metabolic switch during wasp and bacterial infection in Drosophila. In the present study, our results have confirmed that not only the gene expression level of adenosine receptor, but also energy metabolism pathway are downregulated in the brain of honeybee during DWV infection. Meanwhile, as a signal for energy regulation, adenosine will affect Glutamate – Glutamine cycle related to brain energy metabolism and neurological function due to the shortage of ATP. Further, with adenosine feeding for infected honeybee, we found that honeybee can have higher resistance to DWV infection by promoting the adenosine pathway. Here, we conclude that dysfunctional adenosine pathway and energy metabolism may be caused by DWV infection, and then lead to memory loss in honeybee.