Key result
Inactivation of the autism-associated Meis2 gene in mouse peripheral sensory neurons severely impaired the cardio-inhibitory baroreflex independently of cardiac malformations.
Why the study?
Autism spectrum disorder features impaired cardiovascular sympathovagal regulation and decreased vagal tone, prompting investigation into whether inactivating the ASD-associated Meis2 gene in mouse peripheral sensory neurons affects cardiovascular regulation and baroreflex.
Inactivation of the autism-associated Meis2 gene in mouse peripheral sensory neurons blunts the cardio-inhibitory baroreflex, suggesting a mechanism for the autonomic imbalance observed in autism spectrum disorder.
Leaves open Meis2-autonomic link in autism; no immediate clinical implications from this animal model.
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.
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Roussel et al. (2022) studied Autism Spectrum Disorder (ASD) model / Dysautonomia. Meis2 gene inactivation vs. Wild-type and Isl1+/CRE mice was evaluated on Cardio-inhibitory reflex gain (ΔHR/ΔBP) following norepinephrine injection (p=0.0087). Inactivation of the autism-associated Meis2 gene in mouse peripheral sensory neurons severely impaired the cardio-inhibitory baroreflex independently of cardiac malformations.
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