Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, P.O. Box 22452, Riyadh, Saudi Arabia.
Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Lipids Health Dis. 2018 Aug 31;17(1):205. doi: 10.1186/s12944-018-0850-1.
Abnormal phospholipid metabolism is a major component of many neurodevelopmental disorders including autism. Oral administration of propionic acid (PPA) can produce behavioral abnormalities and biochemical features in rodents similar to those observed in autism and can thus be used as a model to understand impaired brain fatty acid metabolism in autism.
The present study was designed to understand alterations in phospholipid metabolism in the brain of a rodent model of autism and to explore omega-3 and vitamin B12 as remedies. Five groups of rats were selected: Group 1 was the control. Group 2 was the rodent model of autism treated with a neurotoxic dose of PPA. Group 3 was given vitamin B12 cobalamin (16.7 mg/kg/day) for 30 days after PPA treatment. Group 4 was given pharmaceutical grade Omega-3 (200 mg cholesterol free-DHA/kg body weight/day), a product of Madre lab, Germany, for 30 days after PPA treatment for 3 days. Group 5 was given a combined dose of ω-3 + Vitamin B12 for the same duration post-PPA treatment. Phospholipid levels and Phospholipase A2 were measured in the brain homogenates of all the groups. ELISA and western blotting were used to detect the cPLA2 protein level.
A significant decrease in phospholipid levels and a significant increase in cPLA2 were found in brain tissue of PPA-treated rats; however, both ω-3 and vitamin B12 were efficient in ameliorating the neurotoxic effect of PPA.
Both ω-3 and vitamin B12 may play a role in ameliorating impaired phospholipid metabolism in autism; however, proper clinical trials are needed.
异常的磷脂代谢是包括自闭症在内的许多神经发育障碍的主要组成部分。丙酸（PPA）的口服给药可以在啮齿动物中产生类似于自闭症中观察到的行为异常和生化特征，因此可以用作理解自闭症中受损大脑脂肪酸代谢的模型。
本研究旨在了解自闭症啮齿动物模型中大脑磷脂代谢的变化，并探索ω-3 和维生素 B12 作为治疗方法。选择了五组大鼠：第 1 组为对照组。第 2 组为用神经毒性剂量 PPA 处理的自闭症啮齿动物模型。第 3 组在 PPA 治疗后 30 天给予维生素 B12 钴胺素（16.7mg/kg/天）。第 4 组给予 Madre lab 德国制药级ω-3（200mg 无胆固醇-DHA/kg 体重/天），在 PPA 治疗后 30 天内连续 3 天给予。第 5 组在 PPA 治疗后相同时间内给予 ω-3+维生素 B12 联合剂量。测量所有组的脑匀浆中的磷脂水平和磷脂酶 A2。使用 ELISA 和 Western blot 检测 cPLA2 蛋白水平。
在 PPA 处理的大鼠脑组织中发现磷脂水平显著降低，cPLA2 显著增加；然而，ω-3 和维生素 B12 都能有效改善 PPA 的神经毒性作用。
ω-3 和维生素 B12 均可改善自闭症中受损的磷脂代谢；然而，需要进行适当的临床试验。
