The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice
Abstract Recent understanding of Autism Spectrum Disorder (ASD) showed that peripheral primary mechanosensitive neurons involved in touch sensation and central neurons affected in ASD share transcriptional regulators. Mutant mice for ASD-associated transcription factors exhibit impaired primary tact...
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| Format: | Article |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24616-5 |
| _version_ | 1797986724973903872 |
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| author | J. Roussel R. Larcher P. Sicard P. Bideaux S. Richard F. Marmigère J. Thireau |
| author_facet | J. Roussel R. Larcher P. Sicard P. Bideaux S. Richard F. Marmigère J. Thireau |
| author_sort | J. Roussel |
| collection | DOAJ |
| description | Abstract Recent understanding of Autism Spectrum Disorder (ASD) showed that peripheral primary mechanosensitive neurons involved in touch sensation and central neurons affected in ASD share transcriptional regulators. Mutant mice for ASD-associated transcription factors exhibit impaired primary tactile perception and restoring those genes specifically in primary sensory neurons rescues some of the anxiety-like behavior and social interaction defects. Interestingly, peripheral mechanosensitive sensory neurons also project to internal organs including the cardiovascular system, and an imbalance of the cardio-vascular sympathovagal regulation is evidenced in ASD and intellectual disability. ASD patients have decreased vagal tone, suggesting dysfunction of sensory neurons involved in cardio-vascular sensing. In light of our previous finding that the ASD-associated Meis2 gene is necessary for normal touch neuron development and function, we investigated here if its inactivation in mouse peripheral sensory neurons also affects cardio-vascular sympathovagal regulation and baroreflex. Combining echocardiography, pharmacological challenge, blood pressure monitoring, and heart rate variability analysis, we found that Meis2 mutant mice exhibited a blunted vagal response independently of any apparent cardiac malformation. These results suggest that defects in primary sensory neurons with mechanosensitive identity could participate in the imbalanced cardio-vascular sympathovagal tone found in ASD patients, reinforcing current hypotheses on the role of primary sensory neurons in the etiology of ASD. |
| first_indexed | 2024-04-11T07:36:33Z |
| format | Article |
| id | doaj.art-7ce5402f95db4863b7225adfc89ad17d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T07:36:33Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7ce5402f95db4863b7225adfc89ad17d2022-12-22T04:36:43ZengNature PortfolioScientific Reports2045-23222022-11-0112111610.1038/s41598-022-24616-5The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in miceJ. Roussel0R. Larcher1P. Sicard2P. Bideaux3S. Richard4F. Marmigère5J. Thireau6Université de Montpellier, CNRS, Institut des Biomolécules Max MousseronPhyMedExp, Université de Montpellier, INSERM, CNRS, CHRU de MontpellierPhyMedExp, Université de Montpellier, INSERM, CNRS, CHRU de MontpellierPhyMedExp, Université de Montpellier, INSERM, CNRS, CHRU de MontpellierPhyMedExp, Université de Montpellier, INSERM, CNRS, CHRU de MontpellierInstitute for Neurosciences of Montpellier, Université de Montpellier, InsermPhyMedExp, Université de Montpellier, INSERM, CNRS, CHRU de MontpellierAbstract Recent understanding of Autism Spectrum Disorder (ASD) showed that peripheral primary mechanosensitive neurons involved in touch sensation and central neurons affected in ASD share transcriptional regulators. Mutant mice for ASD-associated transcription factors exhibit impaired primary tactile perception and restoring those genes specifically in primary sensory neurons rescues some of the anxiety-like behavior and social interaction defects. Interestingly, peripheral mechanosensitive sensory neurons also project to internal organs including the cardiovascular system, and an imbalance of the cardio-vascular sympathovagal regulation is evidenced in ASD and intellectual disability. ASD patients have decreased vagal tone, suggesting dysfunction of sensory neurons involved in cardio-vascular sensing. In light of our previous finding that the ASD-associated Meis2 gene is necessary for normal touch neuron development and function, we investigated here if its inactivation in mouse peripheral sensory neurons also affects cardio-vascular sympathovagal regulation and baroreflex. Combining echocardiography, pharmacological challenge, blood pressure monitoring, and heart rate variability analysis, we found that Meis2 mutant mice exhibited a blunted vagal response independently of any apparent cardiac malformation. These results suggest that defects in primary sensory neurons with mechanosensitive identity could participate in the imbalanced cardio-vascular sympathovagal tone found in ASD patients, reinforcing current hypotheses on the role of primary sensory neurons in the etiology of ASD.https://doi.org/10.1038/s41598-022-24616-5 |
| spellingShingle | J. Roussel R. Larcher P. Sicard P. Bideaux S. Richard F. Marmigère J. Thireau The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice Scientific Reports |
| title | The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice |
| title_full | The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice |
| title_fullStr | The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice |
| title_full_unstemmed | The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice |
| title_short | The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice |
| title_sort | autism associated meis2 gene is necessary for cardiac baroreflex regulation in mice |
| url | https://doi.org/10.1038/s41598-022-24616-5 |
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