Cheng Ning, Rho Jong M, Masino Susan A
Departments of Pediatrics, University of Calgary Calgary, AB, Canada.
Departments of Pediatrics, University of CalgaryCalgary, AB, Canada; Clinical Neurosciences, University of CalgaryCalgary, AB, Canada; Physiology and Pharmacology, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of CalgaryCalgary, AB, Canada.
Front Mol Neurosci. 2017 Feb 21;10:34. doi: 10.3389/fnmol.2017.00034. eCollection 2017.
Autism spectrum disorder (ASD) is characterized by deficits in sociability and communication, and increased repetitive and/or restrictive behaviors. While the etio-pathogenesis of ASD is unknown, clinical manifestations are diverse and many possible genetic and environmental factors have been implicated. As such, it has been a great challenge to identify key neurobiological mechanisms and to develop effective treatments. Current therapies focus on co-morbid conditions (such as epileptic seizures and sleep disturbances) and there is no cure for the core symptoms. Recent studies have increasingly implicated mitochondrial dysfunction in ASD. The fact that mitochondria are an integral part of diverse cellular functions and are susceptible to many insults could explain how a wide range of factors can contribute to a consistent behavioral phenotype in ASD. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), used for nearly a century to treat medically intractable epilepsy, has been shown to enhance mitochondrial function through a multiplicity of mechanisms and affect additional molecular targets that may address symptoms and comorbidities of ASD. Here, we review the evidence for the use of metabolism-based therapies such as the KD in the treatment of ASD as well as emerging co-morbid models of epilepsy and autism. Future research directions aimed at validating such therapeutic approaches and identifying additional and novel mechanistic targets are also discussed.
自闭症谱系障碍（ASD）的特征是社交和沟通能力缺陷，以及重复和/或受限行为增加。虽然ASD的病因发病机制尚不清楚，但其临床表现多样，许多可能的遗传和环境因素都与之相关。因此，确定关键的神经生物学机制并开发有效的治疗方法一直是一项巨大的挑战。目前的治疗方法主要针对共病情况（如癫痫发作和睡眠障碍），而核心症状尚无治愈方法。最近的研究越来越多地表明线粒体功能障碍与ASD有关。线粒体是多种细胞功能不可或缺的一部分，且易受多种损伤，这一事实可以解释为何多种因素会导致ASD出现一致的行为表型。与此同时，近一个世纪以来用于治疗药物难治性癫痫的高脂肪、低碳水化合物生酮饮食（KD），已被证明可通过多种机制增强线粒体功能，并影响可能解决ASD症状和共病的其他分子靶点。在此，我们综述了使用基于代谢的疗法（如KD）治疗ASD的证据，以及新兴的癫痫和自闭症共病模型。还讨论了旨在验证此类治疗方法并确定其他新机制靶点的未来研究方向。
