PDF(Sci-hub)
Abstract：
Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.
摘要：
自闭症谱系障碍（ASD）的病理生理学尚未完全了解；然而，已经报道了炎症反应和谷氨酸信号的改变，导致研究针对ASD治疗中免疫谷氨酸能系统的分子。棕榈酰乙醇胺（PEA）是一种天然存在的饱和N-酰基乙醇胺，已被证明可有效控制炎症，抑郁症,癫痫,和痛苦，可能通过对谷氨酸毒性的神经保护作用。这里,我们系统回顾了所有在ASD中检查PEA及其生物行为相关性的人类和动物研究。研究表明ASD中PEA和其他内源性大麻素(ECB)/酰基乙醇胺(AE)的血清/脑水平改变。改变PEA信号对社会暴露的反应和改变的酶的表达/活性负责ECBs/AEs的合成和催化，以及下调过氧化物酶体增殖物激活受体-α（PPAR-α）和大麻素受体靶GPR55mRNA的脑表达，已被报道。应激和暴露于外源性大麻素可能会调节ECBs/AE水平和神经精神疾病候选基因的表达，对ASD有影响。有限的研究表明，补充PEA可以通过改善语言，社会和非社会行为来降低整体自闭症的严重程度。潜在的神经生物学基础包括调节免疫反应，神经炎症，神经营养,凋亡，神经发生，神经可塑性，神经变性,线粒体功能，和微生物群的活动，可能通过过氧化物酶体增殖物激活受体-α（PPAR-α）激活。
