Abstract
Microglial activation is a key modulator of brain vulnerability in response to intra-uterine growth restriction (IUGR). However, the consequences of IUGR on microglial development and the microglial proteome are still unknown. We used a model of IUGR induced by a gestational low-protein diet (LPD) in rats. Microglia, isolated from control and growth-restricted animals at P1 and P4, showed significant changes in the proteome between the two groups. The expression of protein sets associated with fetal growth, inflammation, and the immune response were significantly enriched in LPD microglia at P1 and P4. Interestingly, upregulation of protein sets associated with the oxidative stress response and reactive oxygen species production was observed at P4 but not P1. During development, inflammation-associated proteins were upregulated between P1 and P4 in both control and LPD microglia. By contrast, proteins associated with DNA repair and senescence pathways were upregulated in only LPD microglia. Similarly, protein sets involved in protein retrograde transport were significantly downregulated in only LPD microglia. Overall, these data demonstrate significant and multiple effects of LPD-induced IUGR on the developmental program of microglial cells, leading to an abnormal proteome within the first postnatal days.
Highlights
Intra-uterine growth restriction (IUGR) and prematurity are the two leading complications of human pregnancy: every year, 30 million infants are delivered after IUGR and 15 million are born preterm [1,2]
We investigated the proteomic profile of our samples by evaluating the expression of the various cell-type-markers in CTRL and lowprotein diet (LPD) microglia at P1 and P4
No difference in cell marker expression has been evidenced among experimental groups, meaning that the purity of sorted microglial cell samples appears similar
Summary
Intra-uterine growth restriction (IUGR) and prematurity are the two leading complications of human pregnancy: every year, 30 million infants are delivered after IUGR and 15 million are born preterm [1,2]. These conditions are recognized to be the two main contributors to neonatal brain injury responsible for the neurodevelopmental disorders that affect more than nine million children each year [3,4,5,6,7,8]. Response to injury in the developing brain is usually associated with but not restricted to an inflammatory response of microglia [17]
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