| 摘要: | 癲癇是一種慢性腦部疾病，是大腦皮質中過度且異常的神經元活動所產生的結果。症狀為身體不自主地不斷嚴重抽搐，發作期間會失去意識和知覺且持續時間不定。現有與癲癇相關的生物標誌還不足以建立對癲癇有效的治療策略。因此，在本研究中我們以具有神經保護和抗衰老等特性的菸醯胺單核苷酸(Nicotinamide Mononucleotide, NMN)預處理，再以戊四唑(Pentylenetetrazole, PTZ)誘發斑馬魚產生癲癇，觀察不同濃度NMN (250μg和500μg)對於癲癇導致斑馬魚大腦異常的預防作用，並和已知具有保護神經維生素C(Vit C)跟具有抗自由基能力的乙醯半胱胺酸(Acetylcystein,NAC)為範本進行互相比較。並用液相層析串聯式質譜儀(UPLC-MS)進行代謝體分析，探討NMN對於癲癇預防作用的潛在機制，以此為基礎找出具代表性的癲癇相關生物標誌。根據研究結果證明，NMN對於PTZ誘發斑馬魚癲癇確實具有預防作用，在行為學上可看出有效的減緩癲癇發作的嚴重程度。透過代謝體分析結果得知，
改變最多的代謝體趨式為神經傳導物質(Neurotransmitter)，NMN增加了GABA、谷氨酸(Glutamate)、乙醯膽鹼(Acetylcholine,Ach）、血清素(Serotonin,5-HT）的濃度，降低了去甲變腎上腺素(Normetanephrine,NM）的濃度，讓大腦不受到癲癇更進一步的破壞。從結果中我們可以確定，NMN確實具有預防癲癇的能力，它透過改變神經傳遞物質的濃度，保護大腦神經免受癲癇的破壞。
Epilepsy is a chronic brain disorder that results from excessive and abnormal neuronal activity in the cerebral cortex. Symptoms are involuntary repeated severe convulsions of the body, during which there is loss of consciousness and consciousness and lasts indefinitely. Existing epilepsy-related biomarkers are insufficient to establish effective therapeutic strategies for epilepsy. Therefore, in this study, we pretreated zebrafish with neuroprotective and anti-aging properties such as nicotinamide mononucleotide (NMN), and then induced epilepsy in zebrafish with pentylenetetrazole (PTZ). The preventive effect of different concentrations of NMN (250μg and 500μg) on epilepsy-induced brain abnormalities in zebrafish, and known to have neuroprotective vitamin C (Vit C) and acetylcysteine (Acetylcystein, NAC) with anti-free radical ability Compare the templates with each other. Metabolite analysis was performed with liquid chromatography tandem mass spectrometry (UPLC-MS) to explore the potential mechanism of NMN's preventive effect on epilepsy, and on this basis to find representative epilepsy-related biomarkers. According to the research results, it is proved that NMN does have a preventive effect on PTZ-induced zebrafish epilepsy, and it can be seen in behavior that it can effectively slow down the severity of epileptic seizures. According to the results of metabolite analysis,
The most changed metabolite is neurotransmitter, NMN increases the concentration of GABA, glutamate, acetylcholine (Ach), serotonin (Serotonin, 5-HT), reduces Increase the concentration of norepinephrine (Normetanephrine, NM), so that the brain is not further damaged by epilepsy. From the results, we can confirm that NMN does have the ability to prevent epilepsy. It protects the brain nerves from the damage of epilepsy by changing the concentration of neurotransmitters. |
