title: Prenatal administration of lipopolysaccharide induces sex-dependent changes in glutamic acid decarboxylase and parvalbumin in the adult rat brain.
abstract: BACKGROUND
  Recent clinical studies suggest GABA-ergic system abnormalities as a neuropathological mechanism of schizophrenia.
  
  
  OBJECTIVE
  In the present study, we examined the effect of chronic prenatal lipopolysaccharide (LPS) administration on immunohistochemical changes of glutamate decarboxylase (GAD67) and parvalbumin (PV)-expressing neurons in the medial prefrontal cortex and hippocampus of rats.
  
  
  RESULTS
  These data demonstrated that prenatal LPS administration during the final 2 weeks of pregnancy induced schizophrenia-like behavioral symptoms, such as deficits in sensorimotor gating (prepulse inhibition) and impairments in social interactions and exploration, in adult offspring. Moreover, immunohistochemical analysis revealed that in our neurodevelopmental model of schizophrenia, decreases in the total number of PV- and GAD67-positive neurons in the medial prefrontal cortices of adult females prenatally exposed to LPS were observed, whereas these immunochemical changes were primarily detected in the hippocampus of males. Additionally, a decrease in PV-labeled axon terminals of GABA-ergic cells, likely reflecting the perisomatic inhibitory innervation of pyramidal neurons, was observed in the medial prefrontal cortices in both sexes.
  
  
  CONCLUSIONS
  This study provided evidence of a key role for the GABA system in neurodevelopment associated with the etiopathogenesis of schizophrenia and showed that the observed changes are sex-dependent. Moreover, this study is the first to present a model of schizophrenia based on prenatal LPS administration, which not only produced behavioral abnormalities but also changed the cytoarchitecture of the GABA inhibitory system.
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. Electronic address: basta@if-pan.krakow.pl.
authors.forename: A
authors.initials: A
authors.lastname: Basta-Kaim
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Fijał
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Ślusarczyk
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Trojan
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Głombik
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Budziszewska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Leśkiewicz
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Regulska
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Kubera
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Lasoń
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Wędzony
mesh_terms: D000818:Animals; D002452:Cell Count; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D010320:Parvalbumins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D065808:Prepulse Inhibition / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D012737:Sex Factors; D012919:Social Behavior
chemical_list: D008070:Lipopolysaccharides; D010320:Parvalbumins; D005968:Glutamate Decarboxylase
keywords: glutamic acid decarboxylase (GAD67); neurodevelopmental model of schizophrenia; parvalbumin (PV); sensorimotor gating; social interaction