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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00422

Molecular Pathology and Pharmacological Treatment of Autism Spectrum Disorder-Like Phenotypes using Rodent Models

  • 1National Yang-Ming University, Taiwan

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with a high prevalence rate. The core symptoms of ASD patients are impaired social communication and repetitive behavior. Genetic and environmental factors contribute to pathophysiology of ASD. Regarding environmental risk factors, it is known that valproic acid (VPA) exposure during pregnancy increases the chance of ASD among offspring. Over a decade of animal model studies have shown that maternal treatment with VPA in rodents recapitulates ASD-like pathophysiology at a molecular, cellular and behavioral level. Here, we review the prevailing theories of ASD pathogenesis, including excitatory/inhibitory imbalance, neurotransmitter dysfunction, dysfunction of mTOR and endocannabinoid signaling pathways, neuroinflammation and epigenetic alterations that have been associated with ASD. We also describe the evidence linking neuropathological changes to ASD-like behavioral abnormalities in maternal VPA-treated rodents. In addition to obtaining an understanding of the neuropathological mechanisms, the VPA-induced ASD-like animal models also serve as a good platform for testing pharmacological reagents that might be use treating ASD. We therefore have summarized the various pharmacological studies that have targeted the classical neurotransmitter systems, the endocannabinoids, the Wnt signal pathway and neuroinflammation. These approaches have been shown to often be able to ameliorate the ASD-like phenotypes induced by maternal VPA treatments.

Keywords: Autism (ASD), Valproic acid (2-propylpentanoic acid), Excitatory/Inhibitory imbalance, endocannabinoids system, MTOR signaling, Wnt signaling, Neuroinflammation, epigenetics

Received: 24 Jul 2018; Accepted: 29 Oct 2018.

Edited by:

Chang-hui Shen, College of Staten Island, United States

Reviewed by:

Elisa L. Hill-Yardin, RMIT University, Australia
Yuriko Iwakura, Niigata University, Japan  

Copyright: © 2018 Kuo and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Fu-Chin Liu, National Yang-Ming University, Taipei, 112, Taiwan, fuchin@ym.edu.tw