Music-Based Intervention Ameliorates <i>Mecp2</i>-Loss-Mediated Sociability Repression in Mice through the Prefrontal Cortex <i>FNDC5/BDNF</i> Pathway
Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investiga...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/13/7174 |
| Summary: | Patients with Rett syndrome (RTT) show severe difficulties with communication, social withdrawl, and learning. Music-based interventions improve social interaction, communication skills, eye contact, and physical skills and reduce seizure frequency in patients with RTT. This study aimed to investigate the mechanism by which music-based interventions compromise sociability impairments in m<i>ecp2</i> <sup>null/y</sup> mice as an experimental RTT model. Male m<i>ecp2</i> <sup>null/y</sup> mice and wild-type mice (24 days old) were randomly divided into control, noise, and music-based intervention groups. Mice were exposed to music or noise for 6 h/day for 3 consecutive weeks. Behavioral patterns, including anxiety, spontaneous exploration, and sociability, were characterized using open-field and three-chamber tests. <i>BDNF</i>, TrkB receptor motif, and <i>FNDC5</i> expression in the prefrontal cortex (PFC), hippocampus, basal ganglia, and amygdala were probed using RT-PCR or immunoblotting. <i>m</i><i>ecp2</i> <sup>null/y</sup> mice showed less locomotion in an open field than wild-type mice. The social novelty rather than the sociability of these animals increased following a music-based intervention, suggesting that music influenced the m<i>ecp2</i>-deletion-induced social interaction repression rather than motor deficit. Mechanically, the loss of <i>BDNF</i> signaling in the prefrontal cortex and hippocampal regions, but not in the basal ganglia and amygdala, was compromised following the music-based intervention in m<i>ecp2</i> <sup>null/y</sup> mice, whereas TrkB signaling was not significantly changed in either region. <i>FNDC5</i> expression in the prefrontal cortex region in m<i>ecp2</i> <sup>null/y</sup> mice also increased following the music-based intervention. Collective evidence reveals that music-based interventions improve m<i>ecp2</i>-loss-induced social dysfunction. <i>BDNF</i> and <i>FNDC5</i> signaling in the prefrontal cortex region mediates the music-based-intervention promotion of social interactions. This study gives new insight into the mechanisms underlying the improvement of social behaviors in mice suffering from experimental Rett syndrome following a music-based intervention. |
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| ISSN: | 1661-6596 1422-0067 |