Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring
Maude Bordeleau, Cesar H. Comin, Lourdes Fernández de Cossío, Chloé Lacabanne, Moises Freitas-Andrade, Fernando González Ibáñez, Joanna Raman-Nair, Michael Wakem, Mallar Chakravarty, Luciano da F. Costa, Baptiste Lacoste, Marie-Ève Tremblay
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.