title: Prenatal LPS-exposure--a neurodevelopmental rat model of schizophrenia--differentially affects cognitive functions, myelination and parvalbumin expression in male and female offspring.
abstract: Maternal infection during pregnancy increases the risk for the offspring to develop schizophrenia. Gender differences can be seen in various features of the illness and sex steroid hormones (e.g. estrogen) have strongly been implicated in the disease pathology. In the present study, we evaluated sex differences in the effects of prenatal exposure to a bacterial endotoxin (lipopolysaccharide, LPS) in rats. Pregnant dams received LPS-injections (100 μg/kg) at gestational day 15 and 16. The offspring was then tested for prepulse inhibition (PPI), locomotor activity, anxiety-like behavior and object recognition memory at various developmental time points. At postnatal day (PD) 33 and 60, prenatally LPS-exposed rats showed locomotor hyperactivity which was similar in male and female offspring. Moreover, prenatal LPS-treatment caused PPI deficits in pubertal (PD45) and adult (PD90) males while PPI impairments were found only at PD45 in prenatally LPS-treated females. Following prenatal LPS-administration, recognition memory for objects was impaired in both sexes with males being more severely affected. Additionally, we assessed prenatal infection-induced alterations of parvalbumin (Parv) expression and myelin fiber density. Male offspring born to LPS-challenged mothers showed decreased myelination in cortical and limbic brain regions as well as reduced numbers of Parv-expressing cells in the medial prefrontal cortex (mPFC), hippocampus and entorhinal cortex. In contrast, LPS-exposed female rats showed only a modest decrease in myelination and Parv immunoreactivity. Collectively, our data indicate that some of the prenatal immune activation effects are sex dependent and further strengthen the importance of taking into account gender differences in animal models of schizophrenia.
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, Hochschulring 18, 28359 Bremen, Germany. Electronic address: wischhof@uni-bremen.de.
authors.forename: Lena
authors.initials: L
authors.lastname: Wischhof
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, Hochschulring 18, 28359 Bremen, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Irrsack
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, Hochschulring 18, 28359 Bremen, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Osorio
authors.affiliation: Brain Research Institute, Department of Neuropharmacology, University of Bremen, Hochschulring 18, 28359 Bremen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006624:Hippocampus; D008070:Lipopolysaccharides / Q000633:toxicity*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism*; D017397:Prefrontal Cortex; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D065808:Prepulse Inhibition / Q000187:drug effects; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology*; D012727:Sex Characteristics
chemical_list: D008070:Lipopolysaccharides; D010320:Parvalbumins
keywords: Cognitive function; GABA; Myelination; Prenatal immune activation; Sex differences