Vascular contribution to a neurodevelopmental disorder

Description

Abstract

While the neuronal underpinnings of autism spectrum disorders (ASD) are being unraveled, vascular contributions to these conditions remain elusive. We investigated postnatal cerebrovascular development in a mouse model of the 16p11.2 deletion ASD syndrome, and discovered that 16p11.2 hemizygosity was causally linked to structural and functional abnormalities of brain vascular networks. Cortical vascular density was reduced at postnatal day (P) 14 in 16p11.2df/+ mice, while baseline cerebral blood flow, neurovascular coupling, and cerebrovascular reactivity were altered at P50. Both developmental and functional vascular deficits were endothelium-dependent. Moreover, network-forming defects were identified in vitro using either 16p11.2df/+ primary mouse brain endothelial cells or human endothelial cells derived from 16p11.2 deletion carriers. We also found that mice with endothelium-specific 16p11.2 haploinsufficiency displayed ASD-associated behavioral traits,including locomotor hyperactivity and increased marble burying. By establishing vascular cells as substantial contributors to 16p11.2 deletion syndrome, our findings open new doors for ASD research.