Biochemistry Department, Science College, King Saud University, Riyadh, Saudi Arabia.
J Neuroinflammation. 2012 Apr 24;9:74. doi: 10.1186/1742-2094-9-74.
Recent clinical observations suggest that certain gut and dietary factors may transiently worsen symptoms in autism. Propionic acid (PA) is a short chain fatty acid and an important intermediate of cellular metabolism. Although PA has several beneficial biological effects, its accumulation is neurotoxic.
Two groups of young Western albino male rats weighing about 45 to 60 grams (approximately 21 days old) were used in the present study. The first group consisted of oral buffered PA-treated rats that were given a neurotoxic dose of 250 mg/kg body weight/day for three days, n = eight; the second group of rats were given only phosphate buffered saline and used as a control. Biochemical parameters representing oxidative stress, energy metabolism, neuroinflammation, neurotransmission, and apoptosis were investigated in brain homogenates of both groups.
Biochemical analyses of brain homogenates from PA-treated rats showed an increase in oxidative stress markers (for example, lipid peroxidation), coupled with a decrease in glutathione (GSH) and glutathione peroxidase (GPX) and catalase activities. Impaired energy metabolism was ascertained through the decrease of lactate dehydrogenase and activation of creatine kinase (CK). Elevated IL-6, TNFα, IFNγ and heat shock protein 70 (HSP70) confirmed the neuroinflammatory effect of PA. Moreover, elevation of caspase3 and DNA fragmentation proved the pro-apoptotic and neurotoxic effect of PA to rat pups
By comparing the results obtained with those from animal models of autism or with clinical data on the biochemical profile of autistic patients, this study showed that the neurotoxicity of PA as an environmental factor could play a central role in the etiology of autistic biochemical features.
最近的临床观察表明，某些肠道和饮食因素可能会使自闭症患者的症状短暂加重。丙酸（PA）是一种短链脂肪酸，也是细胞代谢的重要中间产物。尽管 PA 具有多种有益的生物学效应，但它的积累具有神经毒性。
本研究使用了两组体重约 45 至 60 克（约 21 天大）的年轻西方白化雄性大鼠。第一组为口服缓冲 PA 处理组大鼠，给予 250mg/kg 体重/天的神经毒性剂量，共 3 天，n=8；第二组大鼠仅给予磷酸盐缓冲液，作为对照组。检测两组大鼠脑匀浆中代表氧化应激、能量代谢、神经炎症、神经递质传递和细胞凋亡的生化参数。
PA 处理大鼠脑匀浆的生化分析显示氧化应激标志物（如脂质过氧化）增加，同时谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GPX）以及过氧化氢酶活性降低。通过测定乳酸脱氢酶活性降低和肌酸激酶（CK）的激活，确定能量代谢受损。IL-6、TNFα、IFNγ 和热休克蛋白 70（HSP70）的升高证实了 PA 的神经炎症作用。此外，caspase3 和 DNA 片段的升高证明了 PA 对幼鼠的促凋亡和神经毒性作用。
通过将本研究结果与自闭症动物模型或自闭症患者生化特征的临床数据进行比较，表明 PA 作为环境因素的神经毒性可能在自闭症生化特征的病因学中发挥核心作用。
