title: Prenatal infection leads to ASD-like behavior and altered synaptic pruning in the mouse offspring.
abstract: Environmental challenges to the maternal immune system during pregnancy have been associated with an increase in the frequency of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) appearing in the offspring. Microglia, the brain's resident immune-cells, are now known to be critically involved in normal brain development, shaping connections between neurons by pruning superfluous synaptic spines. Our aim was to investigate whether maternal infection during critical stages of gestation compromises the role of microglia in sculpting neuronal circuits. Using a mouse model of maternal immune activation (MIA) induced by bacterial Lipopolysaccharide (LPS), we assayed the offspring's behavior during postnatal development. Additionally, we quantified spines within the offspring's brain and assessed alterations in some molecular signals involved in pruning. LPS-induced MIA led to behavioral changes relevant to ASD in the offspring in the absence of gross neurological problems. Prenatal LPS resulted in a significant increase in the number of spines in the granule cells of the dentate gyrus, as well as a reduction in hippocampal expression of the fractalkine microglial receptor (CX3CR1), involved in mediating the pruning process in the offspring. Interestingly, these changes were only noted in the male progeny of the LPS challenged dams. These results provide an early indicator that microglial function is altered in the brain of offspring from immune challenged mothers and that the effects in the brain appear to be specific along sex lines.
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Quebec, Canada.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fernández de Cossío
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Quebec, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guzmán
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Quebec, Canada; Nutrition et Neurobiologie Intégrée, INRA UMR 1286, 33076 Bordeaux, France; University of Bordeaux, Bordeaux, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: van der Veldt
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Quebec, Canada. Electronic address: giamal.luheshi@mcgill.ca.
authors.forename: Giamal N
authors.initials: GN
authors.lastname: Luheshi
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000276:immunology* / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia; D065886:Neurodevelopmental Disorders / Q000276:immunology; D009473:Neuronal Plasticity / Q000276:immunology / Q000502:physiology*; D009474:Neurons; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides
keywords: ASD; Complement components; Fractalkine; LPS; Maternal immune activation; Microglia; Synaptic pruning