Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.
PLoS Pathog
; 11(9): e1005140, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26402732
ABSTRACT
The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Complemento C5a
/
Complicaciones Parasitarias del Embarazo
/
Trastornos Neurocognitivos
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Receptor de Anafilatoxina C5a
/
Neurogénesis
/
Interacciones Huésped-Parásitos
/
Malaria
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
PLoS Pathog
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá