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Front. Cell. Neurosci. | doi: 10.3389/fncel.2018.00046

Low-frequency rTMS ameliorates autistic-like behaviors in rats induced by neonatal isolation through regulating the synaptic GABA transmission

 Tao Tan1, Wei Wang1, Haitao Xu2,  Zhilin Huang1, Yu Tian Wang3 and  Zhifang Dong1*
  • 1Chongqing Medical University, China
  • 2Wuhan Yiruide Medical Equipment New Technology Co., Ltd, China
  • 3University of British Columbia, Canada

Patients with autism spectrum disorder (ASD) display abnormalities in neuronal development, synaptic function, and neural circuits. The imbalance of excitatory and inhibitory (E/I) synaptic transmission has been proposed to cause the main behavioral characteristics of ASD. Repetitive transcranial magnetic stimulation (rTMS) can directly or indirectly induce excitability and synaptic plasticity changes in the brain noninvasively. However, whether rTMS can ameliorate autistic-like behaviors in animal model via regulating the balance of E/I synaptic transmission is unknown. By using our recent reported animal model with autistic-like behaviors induced by neonatal isolation (postnatal days 1-9), we found that low-frequency rTMS (LF-rTMS, 1 Hz) treatment for 2 weeks effectively alleviated the acquired autistic-like symptoms, as reflected by an increase in social interaction and decrease in self-grooming, anxiety- and depressive-like behaviors in young adult rats compared to those in untreated animals. Furthermore, the amelioration in autistic-like behavior was accompanied by a restoration of the balance between E/I activity, especially at the level of synaptic transmission and receptors in synaptosomes. These findings indicated that LF-rTMS may alleviate the symptoms of ASD-like behaviors caused by neonatal isolation through regulating the synaptic GABA transmission, suggesting that LF-rTMS may be a potential therapeutic technique to treat ASD.

Keywords: Autism Spectrum Disorders, Neonatal Isolation, Low-frequency repetitive transcranial magnetic stimulation, mIPSCs, GABAAα1R, VGAT.

Received: 15 Nov 2017; Accepted: 12 Feb 2018.

Edited by:

Antonio Gambardella, Magna Græcia University, Italy

Reviewed by:

Lucia Ciranna, Università degli Studi di Catania, Italy
Maximilian Lenz, M.D., Albert Ludwigs Universität Freiburg, Germany  

Copyright: © 2018 Tan, Wang, Xu, Huang, Wang and Dong. 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 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. Zhifang Dong, Chongqing Medical University, Chongqing, China, zfdong@aliyun.com