Institut de Génomique Fonctionnelle, Department of Neuroscience, Stress Hormones and Plasticity Unit, University of Montpellier, INSERM, CNRS, 34090 Montpellier, France.
Institut de Génomique Fonctionnelle, Department of Neuroscience, Stress Hormones and Plasticity Unit, University of Montpellier, INSERM, CNRS, 34090 Montpellier, France; Département de Maieutique, University of Montpellier, 34090 Montpellier, France.
Cell Rep Med. 2024 Nov 19;5(11):101781. doi: 10.1016/j.xcrm.2024.101781. Epub 2024 Oct 17.
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.
针对自闭症谱系障碍和罕见综合征中催产素和血管加压素不足的问题，为治疗社交障碍带来了希望和失望。我们在普瑞德威利综合征和 Schaaf-Yang 综合征的小鼠模型中寻找催产素和血管加压素下游的靶点，这两种疾病均与自闭症的高发病率有关。我们发现了一群外侧隔核神经元，它们在社交接触结束时被激活——根据同伴关系的程度，催产素和血管加压素会抑制这些神经元。这些神经元表达催产素受体，并与 GABA-B 信号偶联，它们被血管加压素兴奋的 GABA 神经元通过 GABA-A 通道抑制。催产素或血管加压素信号的缺失再现了疾病表型。相比之下，通过增加与伴侣和陌生人接触的时间，抑制生长抑素神经元或受体信号可缓解疾病模型的社交障碍。这些发现为神经精神疾病中社交障碍的治疗框架提供了新的见解。
