title: Prenatal versus postnatal maternal factors in the development of infection-induced working memory impairments in mice.
abstract: Prenatal maternal infection is an environmental risk factor for neurodevelopmental psychiatric illness and disease-associated cognitive impairments. Modeling this epidemiological link in animals shows that prenatal immune challenge is capable of inducing long-lasting deficits in numerous cognitive domains. Here, we combined a neonatal cross-fostering design with a mouse model of prenatal immune challenge induced by maternal gestational treatment with the viral mimetic poly(I:C) to dissect the relative contribution of prenatal and postnatal maternal effects on the offspring. We show that offspring prenatally exposed to poly(I:C) display significant impairments in spatial matching-to-position working memory and spatial novelty presence regardless of whether they are raised by gestationally immune-challenged or non-challenged control surrogate mothers. Likewise, prenatally immune challenged offspring exhibit reduced glutamic acid decarboxylase 65-kDa (GAD65) and 67-kDa (GAD67) gene expression in the adult medial prefrontal cortex and dorsal hippocampus largely independently of the postnatal rearing conditions. In addition, we confirm that being raised by a gestationally immune-challenged surrogate mother is sufficient to increase the offspring's locomotor response to systemic amphetamine treatment. Our data thus suggest that prenatal infection-induced deficits in spatial short-term memory are mediated by prenatal maternal effects on the offspring. At the same time, our study adds further weight to the notion that being reared by a surrogate mother that experienced immune activation during pregnancy may constitute a risk factor for specific dopaminergic abnormalities.
authors.affiliation: Center of Neuropharmacology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: Juliet
authors.initials: J
authors.lastname: Richetto
authors.forename: Francesca
authors.initials: F
authors.lastname: Calabrese
authors.forename: Urs
authors.initials: U
authors.lastname: Meyer
authors.forename: Marco A
authors.initials: MA
authors.lastname: Riva
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000172:deficiency* / Q000235:genetics; D006624:Hippocampus / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008569:Memory Disorders / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000037:antagonists & inhibitors / Q000633:toxicity; D011181:Postnatal Care; D017397:Prefrontal Cortex / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011897:Random Allocation; D005680:gamma-Aminobutyric Acid / Q000235:genetics
chemical_list: D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D011070:Poly I-C
keywords: Adoption; Autism; GABA; Glutamic acid decarboxylase; Maternal immune activation; Poly(I:C); Schizophrenia; Working memory