LF-rTMS ameliorates social dysfunction of FMR1 mice via modulating Akt/GSK-3β signaling
Yilin Hou, Jiqian Zhao, Dingding Yang, Runkang Xuan, Rou‐Gang Xie, Mengmeng Wang, Huiming Mo, Lirong Liang, Wenting Wang, Shengxi Wu, Yazhou Wang, Xufeng Liu
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.