title: Maternal immune activation and abnormal brain development across CNS disorders.
abstract: Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies.
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Centre Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Knuesel
authors.affiliation: Brain Ischemia &Regeneration Group, Department of Biomedicine, University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Laurie
authors.initials: L
authors.lastname: Chicha
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Centre Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Britschgi
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Centre Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Schobel
authors.affiliation: Department of Internal Medicine, Emergency Unit, University Hospital, Petersgraben 2, 4031 Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Bodmer
authors.affiliation: The Nisonger Centre, Ohio State University, 1581 Dodd Drive, Columbus, OH 43210, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hellings
authors.affiliation: Pegasus Research, Burggartenstrasse 32, 4103 Bottmingen, Switzerland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Toovey
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Centre Basel, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Prinssen
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology / Q000276:immunology; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000276:immunology; D002493:Central Nervous System Diseases / Q000453:epidemiology* / Q000276:immunology; D002547:Cerebral Palsy / Q000453:epidemiology / Q000276:immunology; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000276:immunology; D005260:Female; D006801:Humans; D010300:Parkinson Disease / Q000453:epidemiology / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology* / Q000276:immunology; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000276:immunology; D012559:Schizophrenia / Q000453:epidemiology / Q000276:immunology