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

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.

Neonatal hyperoxia in mice triggers long-term cognitive deficits via impairments in cerebrovascular function and neurogenesis

“…FISH analysis. Methods were adapted from Bordeleau et al (107). For further details please see the Supplemental Material.…”

The impact of maternal high-fat diet on offspring neurodevelopment

“…In addition, anxiety-like behavior is sometimes associated with the compulsive burying of unharmful objects, such as in the marble-burying test (Taylor et al, 2017). mHFD has been shown to increase the number of buried marbles by young adults, indicative of repetitive compulsive-like behavior (Buffington et al, 2016;Bordeleau et al, 2022) and further supports the notion that mHFD can lead to anxiety-like behaviors in young offspring. As anxiety responses are mostly mediated by the amygdala, unsurprisingly mHFD has been shown to elevate inflammation and disturb GABAergic and serotonergic systems in the amygdala of the offspring (Peleg-Raibstein et al, 2012;Kang et al, 2014;Glendining et al, 2018).…”

“…Furthermore, human studies associate maternal obesity with ADHD in their children (Rodriguez et al, 2008;Rodriguez, 2010;Chen et al, 2014b;Field, 2014). Animals' mHFD models mimic the hyperactivity observed in ADHD cases by increased locomotion activity (Tozuka et al, 2010;Kang et al, 2014;Page et al, 2014;Balsevich et al, 2016;Lippert et al, 2020) and higher repetitive compulsive-like behavior (Buffington et al, 2016;Bordeleau et al, 2022). Moreover, human studies suggest that maternal consumption of HFD during pregnancy and lactation increases the risk of anxiety and depression in children and adolescents (Rodriguez, 2010;Van Lieshout et al, 2013).…”

The impact of maternal dietary folic acid or choline deficiencies on cerebral blood flow, cardiac, aortic, and coronary function in young and middle-aged female mouse offspring following ischemic stroke

“…Further, the NVU is responsible for the maintenance of a highly selective blood-brain barrier (BBB) and cerebral homeostasis, as well as the control of cerebral blood flow (CBF) (79). The impact of maternal diet on the NVU, modulating integrity of cerebral blood vessels and closure of the neural tube, has been established (15,16,(80)(81)(82). Our study adds to these investigations by assessing the hemodynamic response of blood flow within the posterior cerebral artery (PCA) in both young and aged offspring.…”