Bortolozzo-Gleich Maria Helena, Bouisset Guillaume, Geng Lan, Pino Antonia Ruiz, Nomura Yuki, Han Shuting, Li Yulong, Leroy Félix
Instituto de Neurociencias CSIC-UMH, Avenida Santiago Ramon y Cajal, San Juan, de Alicante, Spain.
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.
Nat Commun. 2025 Jul 23;16(1):6783. doi: 10.1038/s41467-025-61994-6.
The neuropeptide arginine-vasopressin (AVP) has been repeatedly associated with the autism spectrum disorder (ASD) but the underlying mechanisms remain unclear. As Shank3B male mice, a model of ASD, exhibit deficits in sociability and social aggression, we focused on the lateral septum (LS), a brain region involved in the regulation of motivated behaviors and observed reduced AVP inputs from the bed nucleus of the stria terminalis (BNST) to LS. Manipulating AVP release from the BNST to LS of wild-type male mice, we found that AVP promotes both sociability and social aggression. Blocking the vasopressin receptor 1a (AVPR1a) in LS impaired sociability, while blocking the receptor 1b (AVPR1b) disrupted social aggression. Consequently, selective activation of AVPR1a or AVPR1b rescued the respective behavioral deficits in Shank3B male mice. These findings reveal that AVP release in LS modulates two distinct social behaviors via different receptors and highlight a possible strategy to rescue sociability during ASD.
神经肽精氨酸加压素（AVP）一直与自闭症谱系障碍（ASD）相关，但潜在机制仍不清楚。由于Shank3B雄性小鼠作为ASD模型，表现出社交能力和社会攻击性缺陷，我们将重点放在外侧隔核（LS），这是一个参与调节动机行为的脑区，并观察到终纹床核（BNST）向LS的AVP输入减少。通过操纵野生型雄性小鼠BNST向LS的AVP释放，我们发现AVP既能促进社交能力，也能促进社会攻击性。阻断LS中的加压素受体1a（AVPR1a）会损害社交能力，而阻断受体1b（AVPR1b）则会破坏社会攻击性。因此，选择性激活AVPR1a或AVPR1b可挽救Shank3B雄性小鼠各自的行为缺陷。这些发现揭示了LS中AVP的释放通过不同受体调节两种不同的社会行为，并突出了一种在ASD期间挽救社交能力的可能策略。
