Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring

Date

2022

Authors

Bordeleau, Maude
Comin, Cesar H.
de Cossío, Lourdes Fernández
Lacabanne, Chloé
Freitas-Andrade, Moises
González Ibáñez, Fernando
Raman-Nair, Joanna
Wakem, Michael
Chakravarty, Mallar
da F. Costa, Luciano

Journal Title

Journal ISSN

Volume Title

Publisher

Communications Biology

Abstract

Various environmental exposures during pregnancy, like maternal diet, can compromise, at critical periods of development, the neurovascular maturation of the offspring. Foetal exposure to maternal high-fat diet (mHFD), common to Western societies, has been shown to disturb neurovascular development in neonates and long-term permeability of the neurovasculature. Nevertheless, the effects of mHFD on the offspring’s cerebrovascular health remains largely elusive. Here, we sought to address this knowledge gap by using a translational mouse model of mHFD exposure. Three-dimensional and ultrastructure analysis of the neurovascular unit (vasculature and parenchymal cells) in mHFD-exposed offspring revealed major alterations of the neurovascular organization and metabolism. These alterations were accompanied by changes in the expression of genes involved in metabolism and immunity, indicating that neurovascular changes may result from abnormal brain metabolism and immune regulation. In addition, mHFD-exposed offspring showed persisting behavioural alterations reminiscent of neurodevelopmental disorders, specifically an increase in stereotyped and repetitive behaviours into adulthood.

Description

In memory of Giamal N. Luheshi who made possible the current study, allowing the people involved to meet, to discuss, and to move forward with the current study. We thank all the team of Dr. Baptiste Lacoste that took the time to share their expertise with M.B. during her training in his lab, as well as Genome-Québec for their service and support in performing the whole-transcript expression experiment by ClariomTM S. We also thank Iris Kim and J. Kasia Szyszkowicz for their technical support with animal handling.

Keywords

blood–brain barrier, neuro-vascular interactions, neuroimmunology

Citation

Bordeleau, M., Comin, C. H., de Cossío, L. F., Lacabanne, C., Freitas-Andrade, M., González Ibáñez, F., ... Tremblay, M-È. (2022). Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring. Communications Biology, 5, 26. https://doi.org/10.1038/s42003-021-02947-9