Oxytocin administration in neonates shapes hippocampal circuitry and restores social behavior in a mouse model of autism.

Publication date: Jul 21, 2021

Oxytocin is an important regulator of the social brain. In some animal models of autism, notably in Magel2-deficient mice, peripheral administration of oxytocin in infancy improves social behaviors until adulthood. However, neither the mechanisms responsible for social deficits nor the mechanisms by which such oxytocin administration has long-term effects are known. Here, we aimed to clarify these oxytocin-dependent mechanisms, focusing on social memory performance. Using in situ hybridization (RNAscope), we have established that Magel2 and oxytocin receptor are co-expressed in the dentate gyrus and CA2/CA3 hippocampal regions involved in the circuitry underlying social memory. Then, we have shown that Magel2-deficient mice, evaluated in a three-chamber test, present a deficit in social memory. Next, in hippocampus, we conducted neuroanatomical and functional studies using immunostaining, oxytocin-binding experiments, ex vivo electrophysiological recordings, calcium imaging and biochemical studies. We demonstrated: an increase of the GABAergic activity of CA3-pyramidal cells associated with an increase in the quantity of oxytocin receptors and of somatostatin interneurons in both DG and CA2/CA3 regions. We also revealed a delay in the GABAergic development sequence in Magel2-deficient pups, linked to phosphorylation modifications of KCC2. Above all, we demonstrated the positive effects of subcutaneous administration of oxytocin in the mutant neonates, restoring hippocampal alterations and social memory at adulthood. Although clinical trials are debated, this study highlights the mechanisms by which peripheral oxytocin administration in neonates impacts the brain and demonstrates the therapeutic value of oxytocin to treat infants with autism spectrum disorders.

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Concepts Keywords
Autism Hippocampus proper
Calcium Oxytocin
Immunostaining Neuropeptides
Mice Neurotransmitters
Models Breastfeeding
G protein-coupled receptors
Endocrine system
Antidiuretics
Drugs
Draft:Oxytocin Receptor Gene
Branches of biology
Hybridization

Semantics

Type Source Name
disease MESH autism
drug DRUGBANK Oxytocin
drug DRUGBANK Calcium
drug DRUGBANK Somatostatin
disease MESH development
disease MESH autism spectrum disorders
drug DRUGBANK Trestolone
drug DRUGBANK Valproic Acid
disease MESH syndromes
drug DRUGBANK Coenzyme M
disease MESH memory deficit
disease MESH anxiety
drug DRUGBANK Proline
drug DRUGBANK Phenoxymethylpenicillin
drug DRUGBANK Isoxaflutole
disease MESH neurodevelopmental disorders
drug DRUGBANK gamma-Aminobutyric acid
drug DRUGBANK Potassium Chloride
drug DRUGBANK Chloride ion
disease MESH pus
drug DRUGBANK Albendazole
disease MESH pathology
disease MESH seizure
disease MESH haploinsufficiency
disease MESH Prader Willi syndrome
disease MESH separated
drug DRUGBANK Vasopressin
drug DRUGBANK Methionine
drug DRUGBANK Staurosporine
disease MESH weaning
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH Rett syndrome
disease MESH schizophrenia
disease MESH social interaction

Original Article

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