Zilkha Virtual Seminar Series: Baptiste Lacoste PhD: “Cerebrovascular and Metabolic Alterations in Autism Spectrum Disorders”

Thursday, September 10, 2020 at 1:00pm to 2:00pm

This is a past event.
Virtual Event

Alterations in vascular processes during brain development may have long-lasting neurodevelopmental consequences, but direct evidence supporting this concept is missing. Autism spectrum disorders (ASD) are neurodevelopmental conditions that affect memory, learning, motor coordination, language and social interactions. While the neuronal underpinnings of ASD are being extensively investigated, whether vascular deficits play a role in ASD onset/progression is unknown. To address this knowledge gap, we investigated the maturation of cerebrovascular networks in 16p11.2df/+ mice, a robust mouse model of the 16p11.2 deletion ASD syndrome. We also achieved endothelial-specific deletion of the 16p11.2 locus (16p11.2EC mice). Using both constitutive and conditional mutants, we quantified neurovascular structure and function in vivo and in vitro, and assessed mouse behavior. We demonstrate that 16p11.2 hemizygosity leads to endothelium-dependent structural and functional neurovascular abnormalities.  In 16p11.2df/+ mice, endothelial dysfunction manifested in impaired cerebral angiogenesis at postnatal day (P) 14, and altered neurovascular function at P50.  Defective angiogenesis was further confirmed in vitro using primary 16p11.2df/+ mouse brain endothelial cells, and also patient-derived endothelial cells from 16p11.2 deletion carriers. Interestingly, mice with endothelium-specific 16p11.2 deletion partially recapitulated ASD behavioral traits, including locomotor hyperactivity and altered motor learning. Finally, our more recent work reveals a brain metabolic shift in both 16p11.2df/+ and 16p11.2EC mice, probably in response to altered cerebrovascular function. By showing that endothelial 16p11.2 homozygosity is required for normal brain maturation and function, our findings identify vascular cells as substantial players in ASD.

Dial-In Information

Meeting ID: 919 4391 4125

Password: 271140

Telephone: +1 669 900 6833 or +1 346 248 7799

Event Type

Lecture / Talk / Workshop

Audience

Students, Alumni, Faculty/Staff

Campus

Health Sciences Campus

Tags

academics

Department
Keck School of Medicine
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