Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2

Laura Caccialupi da Prato (1) , Ugo Zayan (1) , Dina Abdallah (1) , Vanessa Point , Fabienne Schaller (1) , Emilie Pallesi-Pocachard (1) , Aurélie Montheil (1) , Stéphane Canaan (2) , Jean-Luc Gaiarsa (1) , Françoise Muscatelli (1) , Valéry Matarazzo (1)

1 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
2 LISM - Laboratoire d'ingénierie des systèmes macromoléculaires

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.

Mots clés: Autism spectrum disorders; Perception

Domaines: Neurosciences [q-bio.NC]

Laura Caccialupi da Prato, Ugo Zayan, Dina Abdallah, Vanessa Point, Fabienne Schaller, et al.. Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2. Neuropsychopharmacology, In press, ⟨10.1038/s41386-022-01313-5⟩. ⟨hal-03654250⟩