1. Neuropeptide therapeutics to repress lateral septum neurons that disable sociability in an autism mouse model.
- Author
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Borie AM, Dromard Y, Chakraborty P, Fontanaud P, Andre EM, François A, Colson P, Muscatelli F, Guillon G, Desarménien MG, and Jeanneteau F
- Subjects
- Animals, Mice, Receptors, Oxytocin metabolism, Neuropeptides metabolism, Male, Vasopressins metabolism, Somatostatin metabolism, Septal Nuclei drug effects, Septal Nuclei metabolism, Signal Transduction drug effects, Mice, Inbred C57BL, Disease Models, Animal, Neurons metabolism, Neurons drug effects, Social Behavior, Autistic Disorder drug therapy, Autistic Disorder metabolism, Oxytocin pharmacology
- Abstract
Confronting oxytocin and vasopressin deficits in autism spectrum disorders and rare syndromes brought promises and disappointments for the treatment of social disabilities. We searched downstream of oxytocin and vasopressin for targets alleviating social deficits in a mouse model of Prader-Willi syndrome and Schaaf-Yang syndrome, both associated with high prevalence of autism. We found a population of neurons in the lateral septum-activated on termination of social contacts-which oxytocin and vasopressin inhibit as per degree of peer affiliation. These are somatostatin neurons expressing oxytocin receptors coupled to GABA-B signaling, which are inhibited via GABA-A channels by vasopressin-excited GABA neurons. Loss of oxytocin or vasopressin signaling recapitulated the disease phenotype. By contrast, deactivation of somatostatin neurons or receptor signaling alleviated social deficits of disease models by increasing the duration of contacts with mates and strangers. These findings provide new insights into the treatment framework of social disabilities in neuropsychiatric disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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