LF-rTMS ameliorates social dysfunction of FMR1-/- mice via modulating Akt/GSK-3β signaling

Yilin Hou; Jiqian Zhao; Dingding Yang; Runkang Xuan; Rougang Xie; Mengmeng Wang; Huiming Mo; Lirong Liang; Wenting Wang; Shengxi Wu; Yazhou Wang; Xufeng Liu

doi:10.1016/j.bbrc.2021.02.086

LF-rTMS ameliorates social dysfunction of FMR1^-/- mice via modulating Akt/GSK-3β signaling

Biochem Biophys Res Commun. 2021 Apr 23:550:22-29. doi: 10.1016/j.bbrc.2021.02.086. Epub 2021 Mar 5.

Authors

Yilin Hou¹, Jiqian Zhao², Dingding Yang², Runkang Xuan², Rougang Xie², Mengmeng Wang², Huiming Mo³, Lirong Liang⁴, Wenting Wang², Shengxi Wu², Yazhou Wang⁵, Xufeng Liu⁶

Affiliations

¹ Department of Military Psychology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.
² Department of Neurobiology and Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.
³ Department of Physiology, Medicine College of Yanan University, Yan'an, 716000, PR China.
⁴ State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research, Center for Dental Materials and Advanced Manufacture, Department of Anethesiology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China.
⁵ Department of Neurobiology and Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China. Electronic address: yazhouw@fmmu.edu.cn.
⁶ Department of Military Psychology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, PR China. Electronic address: 583466585@qq.com.

PMID: 33677132
DOI: 10.1016/j.bbrc.2021.02.086

Abstract

Autism spectrum disorders (ASD) are a group of neurological disorders which affect approximately 1% of children around the world. Social dysfunction is one of the two core syndromes of ASD, and still lacks effective treatment. Transcranial magnetic stimulation (TMS) is a noninvasive and safe procedure that uses magnetic fields to modulate neural activity. Whether it were effective in modulating social function remains unclear. By using 3-chamber test, ultrasonic vocalization recording and Western-blotting, we demonstrated that FMR1 (fragile X mental retardation protein) mutant mice, a model of ASD, exhibited obvious defects in social preference and ultrasonic communication. In addition, we detected increase of p-Akt (S473) and p-GSK-3β (S9), and decrease of p-PSD-95 (T19) in the anterior cingulate cortex (ACC) of FMR1^-/- mice. Treating FMR1^-/- mice with 1 Hz repetitive TMS (rTMS) exerted a long lasting effect in improving both the ultrasonic communication and social preference, as well as restoring the levels of Akt/GSK-3β activity and spine density in the FMR1^-/-ACC. Our data, for the first time, demonstrated a beneficial effect of low frequency rTMS (LF-rTMS) on the social function of FMR1^-/- mice and an involvement of Akt/GSK-3β signaling in this process, indicating LF-rTMS as a potential therapeutic strategy for ASD patients.

Keywords: Akt/GSK-3β signaling; Autism spectrum disorders; Social behavior; Transcranial magnetic stimulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animal Communication
Animals
Autism Spectrum Disorder / prevention & control
Autism Spectrum Disorder / therapy
Female
Fragile X Mental Retardation Protein / genetics*
Gene Deletion*
Glycogen Synthase Kinase 3 beta / metabolism*
Gyrus Cinguli / metabolism
Male
Mice
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction*
Social Behavior Disorders / prevention & control*
Social Behavior Disorders / therapy*
Time Factors
Transcranial Magnetic Stimulation*
Ultrasonics

Substances

Fmr1 protein, mouse
Fragile X Mental Retardation Protein
Akt1 protein, mouse
Glycogen Synthase Kinase 3 beta
Gsk3b protein, mouse
Proto-Oncogene Proteins c-akt