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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00500

Aberrant development and synaptic transmission of cerebellar cortex in a VPA induced mouse autism model

Ruanna Wang1, Jiahui Tan1, Junxiu Guo2, Qing Han2,  Kwok-fai So2, Jiandong Yu2 and  Li Zhang1*
  • 1Guangdong-Hongkong-Macau Institute for CNS Regeneration, Jinan University, China
  • 2Guangdong-Hongkong-Macau Institute for CNS Regeneration, Jinan University, China

Autistic spectral disorder (ASD) is one prevalent neurodevelopmental disease that affects multiple brain regions. Both clinical and animal studies are revealing the possible involvement of cerebellum in ASD pathology. In this study, we generated a rodent ASD model by single prenatal administration of valproic acid (VPA) into pregnant mice, followed by cerebellar morphological and functional studies on offspring. Behavioral studies showed that VPA exposure led to retardation of critical motor reflexes in juveniles, and impaired learning in a tone-conditioned complex motor task in adults. These behavioral phenotypes were associated with premature migration and excess apoptosis of granular cell (GC) precursor in cerebellar cortex during early postnatal period, and decreased cell density plus impaired dendritic arborization of Purkinje neurons. On acute cerebellar slices, suppressed synaptic transmission of Purkinje cells were reported in VPA mice. In summary, converging evidences from anatomical, electrophysiological and behavioral abnormalities in VPA mice suggest cerebellar pathology in ASD and indicate potential values of motor dysfunction in the early diagnosis of ASD.

Keywords: autism, Cerebellum, Environmental Exposure, motor learning, postnatal development

Received: 10 Sep 2018; Accepted: 03 Dec 2018.

Edited by:

Ying Shen, Zhejiang University, China

Reviewed by:

Laurens Bosman, Erasmus Medical Center, Erasmus University Rotterdam, Netherlands
Simone Astori, École Polytechnique Fédérale de Lausanne, Switzerland  

Copyright: © 2018 Wang, Tan, Guo, Han, So, Yu and Zhang. 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: Dr. Li Zhang, Jinan University, Guangdong-Hongkong-Macau Institute for CNS Regeneration, Guangzhou, China,