title: Maternal immune activation epigenetically regulates hippocampal serotonin transporter levels.
abstract: Major depressive disorder (MDD) is one of the most debilitating psychiatric diseases, affecting a large percentage of the population worldwide. Currently, the underlying pathomechanisms remain incompletely understood, hampering the development of critically needed alternative therapeutic strategies, which further largely depends on the availability of suitable model systems. Here we used a mouse model of early life stress - a precipitating factor for the development of MDD - featuring infectious stress through maternal immune activation (MIA) by polyinosinic:polycytidilic acid (Poly(I:C)) to examine epigenetic modulations as potential molecular correlates of the alterations in brain structure, function and behavior. We found that in adult female MIA offspring anhedonic behavior was associated with modulations of the global histone acetylation profile in the hippocampus. Morevoer, specific changes at the promoter and in the expression of the serotonin transporter (SERT), critically involved in the etiology of MDD and pharmacological antidepressant treatment were detected. Furthermore, an accompanying reduction in hippocampal levels of histone deacetylase (HDAC) 1 was observed in MIA as compared to control offspring. Based on these results we propose a model in which the long-lasting impact of MIA on depression-like behavior and associated molecular and cellular aberrations in the offspring is brought about by the modulation of epigenetic processes and consequent enduring changes in gene expression. These data provide additional insights into the principles underlying the impact of early infectious stress on the development of MDD and may contribute to the development of new targets for antidepressant therapy.
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Sonali N
authors.initials: SN
authors.lastname: Reisinger
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Eryan
authors.initials: E
authors.lastname: Kong
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Deeba
authors.initials: D
authors.lastname: Khan
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ronovsky
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Berger
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Horvath
authors.affiliation: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria.
authors.forename: Maureen
authors.initials: M
authors.lastname: Cabatic
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, Austria.
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Pollak
keywords: Depression; Epigenetics; Histone acetylation; Infectious stress; Maternal immune activation; Serotonin transporter