Onaolapo Adejoke Y, Onaolapo Olakunle J, Nwoha Polycarp U
Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomosho, Oyo State, Nigeria; Department of Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria.
Neurobiol Learn Mem. 2017 Mar;139:76-88. doi: 10.1016/j.nlm.2016.12.021. Epub 2016 Dec 31.
Changes, in behaviour, oxidative markers of stress and hippocampal morphology were evaluated following aspartame administration. Mice, (20-22g each) were given vehicle (10ml/kg) or aspartame (20, 40, 80 and 160mg/kg) daily for 28days. They were tested in the Y-maze, radial-arm maze and elevated plus-maze (EPM) after the first and last dose of vehicle or aspartame; and then sacrificed. Hippocampal slices were analysed for aspartic acid, nitric oxide (NO) and superoxide dismutase (SOD); and processed for general histology and neuritic plaques. Glial fibrillary-acid protein (GFAP) expression and neuron-specific enolase (NSE) activities were determined. Radial-arm maze scores increased significantly after acute administration at 80 and 160mg/kg. Repeated administration at 20 and 40mg/kg (Y-maze) and at 40mg/kg (radial-arm maze) was also associated with increased scores, however, performance decreased at higher doses. EPM tests revealed anxiogenic responses following both acute and repeated administration. Significant increase in SOD and NO activities were observed at 40, 80 and 160mg/kg. Neuron counts reduced at higher doses of aspartame. At 40, 80 and 160mg/kg, fewer GFAP-reactive astrocytes were observed in the cornus ammonis, but increased GFAP-reactivity was observed in the dentate gyrus subgranular zone. NSE-positive neurons were readily identifiable within the dentate gyrus at the lower doses of aspartame; but at 160mg/kg, there was marked neuron loss and reduction in NSE-positive neurons. Oral aspartame significantly altered behaviour, anti-oxidant status and morphology of the hippocampus in mice; also, it may probably trigger hippocampal adult neurogenesis.
在给予阿斯巴甜后，对行为、应激氧化标志物和海马形态的变化进行了评估。小鼠（每只20 - 22克）每天给予溶媒（10毫升/千克）或阿斯巴甜（20、40、80和160毫克/千克），持续28天。在首次和末次给予溶媒或阿斯巴甜后，对它们进行Y迷宫、放射状臂迷宫和高架十字迷宫（EPM）测试；然后处死。分析海马切片中的天冬氨酸、一氧化氮（NO）和超氧化物歧化酶（SOD）；并进行常规组织学和神经炎性斑块处理。测定胶质纤维酸性蛋白（GFAP）表达和神经元特异性烯醇化酶（NSE）活性。在急性给予80和160毫克/千克时，放射状臂迷宫得分显著增加。在20和40毫克/千克（Y迷宫）以及40毫克/千克（放射状臂迷宫）重复给药时得分也增加，然而，在更高剂量时表现下降。EPM测试显示急性和重复给药后均有焦虑反应。在40、80和160毫克/千克时观察到SOD和NO活性显著增加。在较高剂量的阿斯巴甜下神经元数量减少。在40、80和160毫克/千克时，在海马角中观察到较少的GFAP反应性星形胶质细胞，但在齿状回颗粒下区观察到GFAP反应性增加。在较低剂量的阿斯巴甜时，在齿状回内很容易识别出NSE阳性神经元；但在160毫克/千克时，有明显的神经元丢失和NSE阳性神经元减少。口服阿斯巴甜显著改变了小鼠的行为、抗氧化状态和海马形态；此外，它可能会触发海马的成年神经发生。
