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

• Published in: Communications biology Vol. 5; no. 1; p. 26
• Main Authors: Bordeleau, Maude, Comin, Cesar H., Fernández de Cossío, Lourdes, Lacabanne, Chloé, Freitas-Andrade, Moises, González Ibáñez, Fernando, Raman-Nair, Joanna, Wakem, Michael, Chakravarty, Mallar, Costa, Luciano da F., Lacoste, Baptiste, Tremblay, Marie-Ève
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-01-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/51; 14; 14/28; 14/32; 14/63; 45; 45/61; 631/378/1341; 631/378/2607; 631/378/371; 64; 64/60; Animals; Behavior, Animal - physiology; Biology; Biomedical and Life Sciences; Cerebral Cortex - blood supply; Cerebral Cortex - cytology; Cerebral Cortex - pathology; Diet, High-Fat - adverse effects; Female; High fat diet; Immunoregulation; Life Sciences; Male; Maternal Exposure; Metabolism; Mice; Microglia - pathology; Neonates; Neurodevelopmental disorders; Offspring; Permeability; Pregnancy; Prenatal Exposure Delayed Effects; Translation; Ultrastructure
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02947-9

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.
In order to advance our understanding of the effects of maternal high-fat diet (mHFD) on the cerebrovascular health of offspring, Bordeleau et al. use a translational mouse model of mHFD exposure. They demonstrate that mHFD induces cerebrovascular and microglial changes in the offspring as well as behavioural alterations that are reminiscent of neurodevelopmental disorders associated with repetitive behaviours at adulthood.