目的:本研究旨在探讨补充乙酰左旋肉碱在小鼠高同型半胱氨酸血症诱导的AD表现中减轻痴呆和认知能力下降的作用。
背景:阿尔茨海默病(AD)是一种以痴呆为特征的神经系统疾病,和认知能力的退化。天然补充剂作为AD的治疗方法非常受欢迎,由于合成药物的毒性较高。高同型半胱氨酸血症会对皮质神经元产生兴奋毒性,这让我们意识到氨基酸可能会导致胆碱能畸形,是AD的重要病因参数。发现乙酰L-肉碱是甲基供体,存在三个与氮原子连接的化学反应性甲基,具有针对AD实验模型的神经保护活性。
目的:本研究的目的是在小鼠模型中研究和评估乙酰左旋肉碱对高同型半胱氨酸血症诱导的阿尔茨海默病(AD)的药理作用。
方法:将动物分为正常对照(媒介物处理),HHcy(dl-同型半胱氨酸硫内酯治疗)阴性对照,测试组,即,低剂量(50mg/kg,p.o)乙酰L-肉碱(L-ALC),高剂量(100mg/kg,P.o)乙酰L-肉碱(H-ALC),L-ALC+SOV(原钒酸钠)和H-ALC+SOV。HHcy是通过给予dl-同型半胱氨酸硫内酯诱导的(dl-HCT;1g/kg,p.o.)在实验时间表的第1天至第15天,除正常对照外,所有动物。由于神经炎症,动物行为模式的变化,和胆碱能功能障碍在旋转杆检查,新颖的客观识别,被动回避,高架加上迷宫,和Morris水迷宫分析.生化调查包括总同型半胱氨酸(tHcy)的估计,肌酸酐激酶(CK),乙酰胆碱酯酶(AChE),硫代巴比妥酸反应性物质(TBARS),还原型谷胱甘肽(GSH)和IL-6和TNF-α。
结果:在小鼠中补充ALC显著降低了实验动物中HHcy诱导的AD表现。发现ALC和SOV成功地减少了行为异常并减轻了Hcy引起的全身Hcy水平的改变,CK活动,和胆碱能功能障碍,改善小鼠前额叶皮层的生物能量学。
结论:发现ALC可改善HHcy引起的认知障碍,这与系统Hcy水平降低有关,CK,和胆碱能异常。它还可以对抗氧化应激诱导的神经炎症,并减少前额叶皮层的促炎标志物。结果共同表明ALC有可能用作AD药物治疗的补充剂。
OBJECTIVE: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD manifestations in the mouse model.
BACKGROUND: Alzheimer\'s disease (AD) is a neurological disorder that is marked by dementia, and degradation of cognitive abilities. There is great popularity gained by natural supplements as the treatment for AD, due to the higher toxicities of synthetic drugs. Hyperhomocysteinemia causes excitotoxicity to the cortical neurons, which brought us to the point that amino acids possibly have a role in causing cholinergic deformities, which are an important etiological parameter in AD. Acetyl L-Carnitine a methyl donor with the presence of three chemically reactive methyl groups linked to a nitrogen atom was found to possess neuroprotective activity against experimental models of AD.
OBJECTIVE: The objective of the present investigation was to investigate and evaluate the pharmacological effect of Acetyl L-Carnitine against hyperhomocysteinemia induced Alzheimer\'s disease (AD) in the mouse model.
METHODS: The animals were divided into normal control (vehicle-treated), HHcy (dl-Homocysteine thiolactone treated) negative control, test group i.e., low dose (50mg/kg, p.o) of acetyl L-carnitine (L-ALC), high dose (100mg/kg,p.o) of acetyl L-carnitine (H-ALC), L-ALC+SOV (Sodium orthovanadate) and H-ALC+SOV. HHcy was induced by administration of dl-Homocysteine thiolactone (dl-HCT; 1 g/kg, p.o.) on day-1 to day-15 of experimental schedule to all animals except normal control. The changes in the behaviour pattern of the animals due to neuroinflammation, and cholinergic dysfunction were examined in rotarod, novel objective recognition, passive avoidance, elevated plus maze, and morris water maze analysis. Biochemical investigation includes the estimation of total homocysteine (tHcy), Creatinine Kinase (CK), Acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and IL-6 and TNF-α.
RESULTS: Supplementation of ALC in mouse considerably lowered the HHcy-induced AD manifestations in the experimental animals. It was found that ALC and SOV successfully diminished the behaviour abnormalities and lessened the Hcy-induced alteration in systemic Hcy levels, CK activity, and cholinergic dysfunction with improved bioenergetics in the Prefrontal cortex of the mice.
CONCLUSIONS: ALC was found to improve the HHcy-induced cognitive disabilities which was found to be associated with the decreased systemic levels of Hcy, CK, and cholinergic abnormalities. It also combats the oxidative stress-induced neuroinflammation with diminished pro-inflammatory markers in the pre frontal cortex. The outcomes collectively indicate ALC\'s potential to be used as a supplementation in the pharmacotherapy of AD.