title: Effects of two commonly found strains of influenza A virus on developing dopaminergic neurons, in relation to the pathophysiology of schizophrenia.
abstract: Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.
authors.affiliation: Cultivo de Tejidos, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr Carlos G Malbran, Buenos Aires, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Landreau
authors.forename: Pablo
authors.initials: P
authors.lastname: Galeano
authors.forename: Laura R
authors.initials: LR
authors.lastname: Caltana
authors.forename: Luis
authors.initials: L
authors.lastname: Masciotra
authors.forename: Agustín
authors.initials: A
authors.lastname: Chertcoff
authors.forename: A
authors.initials: A
authors.lastname: Pontoriero
authors.forename: Elsa
authors.initials: E
authors.lastname: Baumeister
authors.forename: Marcela
authors.initials: M
authors.lastname: Amoroso
authors.forename: Herminia A
authors.initials: HA
authors.lastname: Brusco
authors.forename: Mónica I
authors.initials: MI
authors.lastname: Tous
authors.forename: Vilma L
authors.initials: VL
authors.lastname: Savy
authors.forename: María del Rosario
authors.initials: Mdel R
authors.lastname: Lores Arnaiz
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: de Erausquin
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000821:virology*; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D021641:Recognition, Psychology / Q000502:physiology; D012559:Schizophrenia / Q000821:virology*