Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway

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A growing body of evidence has established the importance of the in utero environment on neurodevelopment and long-term cognitive and behavioral outcomes. These data suggest factors that disrupt the tightly regulated in utero environment can modify normal neurodevelopmental processes. Approximately 125 million pregnancies worldwide are at risk of malaria infection every year. However the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Here we use a mouse model of malaria in pregnancy to examine the impact of maternal malaria exposure on neurocognitive outcomes in offspring. We observed impaired learning and memory and depressive-like behavior in malaria-exposed offspring that were neither congenitally infected nor low birth weight. These neurocognitive impairments were associated with decreased tissue levels of neurotransmitters in regions of the brain linked to the observed deficits. Disruption of maternal C5a complement receptor signaling restored the levels of neurotransmitters and rescued the associated cognitive phenotype observed in malaria-exposed offspring. This study provides the first evidence implicating a causal link between pre-natal exposure to malaria, complement signaling and subsequent neurocognitive impairment in offspring.

Vyšlo v časopise: Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005140
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005140

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