An ASXL3-thyroid hormone axis in parvalbumin interneurons controls autism-like behaviors.

Loss of ASXL3 causes ASD-like behaviors by expanding parvalbumin interneurons through disrupted thyroid hormone signaling in mice.

• Why it matters: Understanding how genetic variants like ASXL3 influence neural circuits is crucial for developing targeted therapies for autism spectrum disorder, especially since the mechanisms are not fully known.
• What they did: The study used mouse models with Asxl3 haploinsufficiency, examining cortical structure, interneuron populations, and behavioral outcomes, and tested neonatal versus adolescent thyroid hormone supplementation.
• The result: Neonatal thyroid hormone treatment restored interneuron numbers and behaviors, while reintroducing ASXL3 via AAV normalized brain architecture, highlighting a critical early intervention window and a targetable ASXL3-TH-PV pathway.