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

Maude Bordeleau,Moises Freitas-Andrade,Joanna Raman-Nair,Luciano Da F Costa,Marie-Ève Tremblay,Lourdes Fernández De Cossío,Chloé Lacabanne,Michael Wakem,Mallar Chakravarty,Cesar H Comin,Fernando González Ibáñez,Baptiste Lacoste

doi:10.1038/s42003-021-02947-9

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.

Highlights

Various environmental exposures during pregnancy, like maternal diet, can compromise, at critical periods of development, the neurovascular maturation of the offspring
These parameters remained unchanged in the maternal high-fat diet (mHFD)-exposed offspring (Supplementary Table 1), suggesting that hypervascularization of the cerebrovasculature was not associated with major dysfunction of cortical endothelial cells
We evaluated the impact of mHFD on Iba1-positive (+) microglial density, average distance to blood vessels, and ratio of cells contacting a vessel during adolescence

Summary

Introduction

Various environmental exposures during pregnancy, like maternal diet, can compromise, at critical periods of development, the neurovascular maturation of the offspring. To evaluate whether this change in cortical cerebrovascular system organisation was associated with functional alterations of blood vessels, we characterised the ultrastructural properties of capillaries in the parietal cortex by quantifying the area of the endothelium, basement membrane thickness, number of mitochondria, fusion/fission rate of mitochondria, as well as number, length, and thickness of tight junctions (Supplementary Fig. 1c).

Results

Conclusion