The long-term consequences of maternal LPS exposure

LPS, lipopolysaccharide, or better lipopolysaccharides are a group of large molecules consisting of a lipid attached to a polysaccharide. They are found on the outer cell membrane of Gram-negative bacteria and act as an endotoxin. It binds to the CD14/TLR4/MD2 receptor complex that can be found on the membrane of several immune cells (monocytes, dendritic cells, macrophages and B cells). Like PolyI:C, prenatal LPS, while not crossing the blood placental barrier, activates the maternal immune system which ultimately affect the foetus.

We currently have two projects aimed at investigating the long-term consequences of prenatal LPS treatment. In the first project, we specifically investigate how the timing of the maternal immune activation affects behaviour. Specifically, we have exposed pregnant rats to two consecutive injections of LPS on gestational days 10 and 11, 15 and 16 or 18 and 19. We have found that exposure on gestational days 10 and 11 (but not 15/16 or 18/19) leads to cognitive deficits in, among others, working memory capacity and selective attention. Additionally, we found that exposure of gestational days 15 and 16 (but not 10/11 and 18/19) leads to emotional deficits in, among others, reward sensitivity anticipatory pleasure and social interaction.

In the second project, we investigate the epigenetic changes induced by LPS. Specifically, we aim to perform both a targeted and a genome wide methylation approach. DNA methylation involves the addition of a methyl group on specific DNA nucleotides, typically (though not exclusively) cytosines. In most situations, DNA methylation leads to transcriptional repression, and thus to a reduction in protein production. By investigating different brain regions after LPS administration on gestational days 10 and 11 or 15 and 16, we hope to gain more insight into the neurobiological basis of the cognitive and emotional deficits induced by prenatal LPS.

This research is in part sponsored by a grant from the Neurological Foundation.

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