Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?

• Main Authors: Asher Ornoy, Liza Weinstein-Fudim, Zivanit Ergaz
• Format: Article
• Language: English
• Published: MDPI AG 2019-03-01
• Series: International Journal of Molecular Sciences
• Subjects: animal models of ASD; rodents; amelioration; prevention; VPA; oxytocin; SAM; PUFAs; human ASD
• Online Access: http://www.mdpi.com/1422-0067/20/5/1074

Since the first animal model of valproic acid (VPA) induced autistic-like behavior, many genetic and non-genetic experimental animal models for Autism Spectrum Disorder (ASD) have been described. The more common non-genetic animal models induce ASD in rats and mice by infection/inflammation or the prenatal or early postnatal administration of VPA. Through the establishment of these models, attempts have been made to ameliorate or even prevent ASD-like symptoms. Some of the genetic models have been successfully treated by genetic manipulations or the manipulation of neurotransmission. Different antioxidants have been used (i.e., astaxanthin, green tea, piperine) to reduce brain oxidative stress in VPA-induced ASD models. Agents affecting brain neurotransmitters (donepezil, agmatine, agomelatine, memantine, oxytocin) also successfully reduced ASD-like symptoms. However, complete prevention of the development of symptoms was achieved only rarely. In our recent study, we treated mouse offspring exposed on postnatal day four to VPA with S-adenosine methionine (SAM) for three days, and prevented ASD-like behavior, brain oxidative stress, and the changes in gene expression induced by VPA. In this review, we describe, in addition to our data, the existing literature on the prevention/amelioration of ASD-like symptoms. We also discuss the possible mechanisms underlying some of these phenomena. Finally, we describe some of the clinical trials in children with ASD that were carried out as a result of data from animal studies, especially those with polyunsaturated fatty acids (PUFAs).