Calling out. Oxytocin is a key component of the mother-infant bound. Here, the authors show that in a mouse model of autism, Magel2 ko, newborns do not call out for their dam when exposed to cold. The deficit is not sensory per se, nor metabolic. Instead, sensory inputs do not trigger the appropriate behavioral response. The authors demonstrate that this depends on the activation of the oxytocin pathway and that intranasal administrations in the mutant pups rescue it, suggesting the benefits of such approach in patients. (I.B.)
Authors: L Caccialupi Da Prato, U Zayan, D Abdallah, V Point, F Schaller, E Pallesi-Pocachard, A Montheil, S Canaan, J-L Gaiarsa, F Muscatelli & V Matarazzo
Scientific abstract: Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.
Published in Neuropsychopharmacology, 2022