Promising Repetitive unidirectional Spinal Tactile Stimulation Promotes Microglial Synaptic Modulation in mPFC of ASD Mouse through Bmal1 DOI
Y. J. Chen, Shuai Zhao, Mingxin Hu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 16, 2025

Abstract Background Synaptic abnormalities are hallmark pathological features of autism spectrum disorders (ASD), contributing to the behavioral impairments frequently observed in these neurodevelopmental conditions. Microglia, as brain’s primary immune cells, essential for synaptic refinement during adolescent development. Disrupted microglial-mediated pruning has been implicated pathophysiology ASDs, however, underlying mechanisms remain incompletely elucidated. In this context, repetitive unidirectional spinal tactile stimulation (RSTS) emerged a promising non-invasive therapeutic strategy. By delivering gentle, skin surface over region, RSTS shown modulate microglial function and effectively restore balance.Objective This study aims explore how enhances medial prefrontal cortex (mPFC) development ASD mice, with specific focus on role Brain Muscle ARNT-Like 1 (Arntl1), core circadian protein crucial regulating process.Methods mice underwent treatment brain 21 days, administered twice daily 10 minutes per session. Behavioral changes were evaluated using three-chamber social interaction open field tests. Synapse number morphology assessed through Golgi staining. To determine effects development, expression analyzed immunofluorescence staining Western blot. Furthermore, molecular mechanism synapse implications comprehensively investigated single-nucleus RNA sequencing (snRNA-seq) chromatin immunoprecipitation (ChIP-seq). Finally, Bmal1 was validated Bmal1 knockout confirming its involvement enhancement by ASD.Results found alleviate autistic-like behaviors Results from snRNA-seq ChIP-seq analyses indicated that may be mediated transcriptional regulation pruning. vivo experiments confirmed mPFC via Bmal1. These findings suggested serves critical target facilitating developmental period mice.Conclusion represents first comprehensive investigation into treating ASD, utilizing single-cell sequencing, gene-knockout complementary analyses. Our suggest potentially modulation Bmal1-dependent key proteins complement system. results provide novel empirical evidence restoring balance offer valuable insights potential an intervention further elucidating regulatory pathways which contributes disorders.

Language: Английский

Promising Repetitive unidirectional Spinal Tactile Stimulation Promotes Microglial Synaptic Modulation in mPFC of ASD Mouse through Bmal1 DOI
Y. J. Chen, Shuai Zhao, Mingxin Hu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 16, 2025

Abstract Background Synaptic abnormalities are hallmark pathological features of autism spectrum disorders (ASD), contributing to the behavioral impairments frequently observed in these neurodevelopmental conditions. Microglia, as brain’s primary immune cells, essential for synaptic refinement during adolescent development. Disrupted microglial-mediated pruning has been implicated pathophysiology ASDs, however, underlying mechanisms remain incompletely elucidated. In this context, repetitive unidirectional spinal tactile stimulation (RSTS) emerged a promising non-invasive therapeutic strategy. By delivering gentle, skin surface over region, RSTS shown modulate microglial function and effectively restore balance.Objective This study aims explore how enhances medial prefrontal cortex (mPFC) development ASD mice, with specific focus on role Brain Muscle ARNT-Like 1 (Arntl1), core circadian protein crucial regulating process.Methods mice underwent treatment brain 21 days, administered twice daily 10 minutes per session. Behavioral changes were evaluated using three-chamber social interaction open field tests. Synapse number morphology assessed through Golgi staining. To determine effects development, expression analyzed immunofluorescence staining Western blot. Furthermore, molecular mechanism synapse implications comprehensively investigated single-nucleus RNA sequencing (snRNA-seq) chromatin immunoprecipitation (ChIP-seq). Finally, Bmal1 was validated Bmal1 knockout confirming its involvement enhancement by ASD.Results found alleviate autistic-like behaviors Results from snRNA-seq ChIP-seq analyses indicated that may be mediated transcriptional regulation pruning. vivo experiments confirmed mPFC via Bmal1. These findings suggested serves critical target facilitating developmental period mice.Conclusion represents first comprehensive investigation into treating ASD, utilizing single-cell sequencing, gene-knockout complementary analyses. Our suggest potentially modulation Bmal1-dependent key proteins complement system. results provide novel empirical evidence restoring balance offer valuable insights potential an intervention further elucidating regulatory pathways which contributes disorders.

Language: Английский

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