title: Maternal immune activation transgenerationally modulates maternal care and offspring depression-like behavior.
abstract: Gestational infection is increasingly being recognized for its involvement as causative mechanism in severe developmental brain abnormalities and its contribution to the pathogenesis of psychopathologies later in life. First observations in the widely accepted maternal immune activation (MIA) model based upon the systemic administration of the viral mimetic Polyinosinic:polycytidylic acid (poly(I:C)) have recently suggested a transmission of behavioral and transcriptional traits across generations. Although maternal care behavior (MCB) is known as essential mediator of the transgenerational effects of environmental challenges on offspring brain function and behavior, the possible propagation of alterations of MCB resulting from MIA to following generations has not yet been examined. Here we show that poly(I:C) stimulation at embryonic day 12.5 (E12.5) leads to aberrant MCB and that this effect is transmitted to the female F1 offspring. The transgenerational effects on MCB are paralleled by enhanced depression-like behavior in the second generation F2 offspring with contributions of both maternal and paternal heritages. Examination of offspring hippocampal expression of genes known as targets of MCB and relevant for ensuing non-genetic transmission of altered brain function and behavior revealed transgenerationally conserved and modified expressional patterns in the F1 and F2 generation. Collectively these data firstly demonstrate the transgenerational transmission of the impact of gestational immune activation on the reproductive care behavior of the mother. Behavioral and molecular characteristics of first and second generation offspring suggest transgenerationally imprinted consequences of gestational infection on psychopathological traits related to mood disorders which remain to be examined in future cross-fostering experiments.
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ronovsky
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Berger
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria.
authors.forename: Alice
authors.initials: A
authors.lastname: Zambon
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria.
authors.forename: Sonali N
authors.initials: SN
authors.lastname: Reisinger
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Horvath
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria.
authors.forename: Arnold
authors.initials: A
authors.lastname: Pollak
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lindtner
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Berger
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria. Electronic address: daniela.pollak@meduniwien.ac.at.
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Pollak
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001927:Brain Diseases; D016207:Cytokines / Q000276:immunology; D003863:Depression / Q000276:immunology*; D003866:Depressive Disorder / Q000276:immunology; D004195:Disease Models, Animal; D005191:Family Characteristics; D005260:Female; D059647:Gene-Environment Interaction; D008297:Male; D008425:Maternal Behavior / Q000502:physiology; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology
chemical_list: D016207:Cytokines; D011070:Poly I-C
keywords: Depression; Epigenetics; Glucocorticoid receptor; Hippocampus; Maternal care behavior; Maternal immune activation; Mineralocorticoid receptor; Oxytocin receptor; Transgenerational