Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
Environ Toxicol Pharmacol. 2018 Sep;62:120-131. doi: 10.1016/j.etap.2018.07.005. Epub 2018 Jul 7.
Metal ions are crucial for normal neurochemical signaling and perturbations in their homeostasis have been associated with neurodegenerative processes. Hypothesizing that in vivo modulation of key neurochemical processes including metal ion regulation (by transferrin receptor-1: TfR-1) in cells can improve disease outcome, we investigated the efficacy of a complex vitamin supplement (CVS) containing B-vitamins and ascorbic acid in preventing/reversing behavioral decline and neuropathology in rats. Wistar rats (eight weeks-old) were assigned into five groups (n = 8), including controls and those administered CVS (400 mg/kg/day) for two weeks before or after AlCl (100 mg/kg)-induced neurotoxicity. Following behavioral assessments, prefrontal cortex (PFC) and hippocampus were prepared for biochemical analyses, histology and histochemistry. CVS significantly reversed reduction of exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety. These correlated with CVS-dependent modulation of TfP-1 expression that were accompanied by significant reversal of neural oxidative stress in expressed superoxide dismutase, nitric oxide, catalase, glutathione peroxidase and malondialdehyde. Furthermore, CVS inhibited neural bioenergetics dysfunction, with increased labelling of glucokinase within PFC and hippocampus correlating with increased glucose-6-phosphate dehydrogenase and decreased lactate dehydrogenase expressions. These relates to inhibition of over-expressed acetylcholinesterase and increased total protein synthesis. Histological and Nissl staining of thin sections corroborated roles of CVS in reversing AlCl-induced neuropathology. Summarily, we showed the role of CVS in normalizing important neurochemical molecules linking concurrent progression of oxidative stress, bioenergetics deficits, synaptic dysfunction and cellular hypertrophy during neurodegeneration.
金属离子对正常的神经化学信号传递至关重要，其体内平衡的紊乱与神经退行性过程有关。我们假设，包括细胞内金属离子调节（通过转铁蛋白受体 1：TfR-1）在内的关键神经化学过程的体内调节，可以改善疾病的预后，因此研究了一种含有 B 族维生素和抗坏血酸的复合维生素补充剂（CVS）在预防/逆转大鼠行为下降和神经病理学方面的疗效。Wistar 大鼠（八周龄）分为五组（n=8），包括对照组和在 AlCl（100mg/kg）诱导神经毒性前或后两周给予 CVS（400mg/kg/天）的大鼠。行为评估后，制备前额叶皮层（PFC）和海马进行生化分析、组织学和组织化学分析。CVS 显著逆转了探索/工作记忆、额叶依赖运动缺陷、认知下降、记忆功能障碍和焦虑。这与 CVS 依赖性调节 TfP-1 表达相关，同时伴随着超氧化物歧化酶、一氧化氮、过氧化氢酶、谷胱甘肽过氧化物酶和丙二醛表达的神经氧化应激的显著逆转。此外，CVS 抑制了神经生物能学功能障碍，在 PFC 和海马中葡萄糖激酶的标记增加，与葡萄糖-6-磷酸脱氢酶的增加和乳酸脱氢酶的减少相关。这与乙酰胆碱酯酶的过度表达抑制和总蛋白质合成增加有关。薄片的组织学和尼氏染色证实了 CVS 在逆转 AlCl 诱导的神经病理学方面的作用。总之，我们表明 CVS 在正常化重要神经化学分子方面发挥作用，这些分子与神经退行性过程中氧化应激、生物能学缺陷、突触功能障碍和细胞肥大的同时进展有关。
