A Vascular-Centric Approach to Autism Spectrum Disorders

Julie Ouellette; Elizabeth E Crouch; Jean-Luc Morel; Vanessa Coelho-Santos; Baptiste Lacoste

doi:10.1177/26331055241235921

A Vascular-Centric Approach to Autism Spectrum Disorders

Neurosci Insights. 2024 Mar 11:19:26331055241235921. doi: 10.1177/26331055241235921. eCollection 2024.

Authors

Julie Ouellette^{1

2}, Elizabeth E Crouch^{3

4}, Jean-Luc Morel^{5

6}, Vanessa Coelho-Santos^{7

8

9}, Baptiste Lacoste^{1

2

10}

Affiliations

¹ Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
² Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
³ Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
⁴ The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
⁵ University Bordeaux, CNRS, INCIA, UMR 5287, Bordeaux, France.
⁶ University Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
⁷ Institute for Nuclear Sciences Applied to Health, University of Coimbra, Coimbra, Portugal.
⁸ Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal.
⁹ Faculty of Medicine, Institute of Physiology, University of Coimbra, Coimbra, Portugal.
¹⁰ University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.

Abstract

Brain development and function are highly reliant on adequate establishment and maintenance of vascular networks. Early impairments in vascular health can impact brain maturation and energy metabolism, which may lead to neurodevelopmental anomalies. Our recent work not only provides novel insights into the development of cerebrovascular networks but also emphasizes the importance of their well-being for proper brain maturation. In particular, we have demonstrated that endothelial dysfunction in autism spectrum disorders (ASD) mouse models is causally related to altered behavior and brain metabolism. In the prenatal human brain, vascular cells change metabolic states in the second trimester. Such findings highlight the need to identify new cellular and molecular players in neurodevelopmental disorders, raising awareness about the importance of a healthy vasculature for brain development. It is thus essential to shift the mostly neuronal point of view in research on ASD and other neurodevelopmental disorders to also include vascular and metabolic features.

Keywords: Autism; angiogenesis; cerebrovascular; endothelium; metabolism; neurodevelopment.