title: Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia.
abstract: Increasing evidence associates schizophrenia with prenatal exposure to infection. Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) of the acoustic startle reflex. We analyzed the effect of a prenatal immune challenge- peripheral administration of bacterial endotoxin lipopolysaccharide (LPS) to pregnant female rats-upon PPI and immune function in adult offspring. Prenatal LPS treatment disrupted PPI which was reversed by antipsychotics. Serum levels of interleukin-2 and interleukin-6 were increased. In addition, histopathological features in brain areas related with PPI circuitry were observed. These results illustrate the critical influence of prenatal immune events upon adult CNS functioning in association with the putative role of the immune system in the etiopathogenesis of schizophrenia.
authors.affiliation: Psychobiology Group, Neural Plasticity Department, Cajal Institute, 28002, Madrid, Spain. cgjb@cajal.csic.es
authors.forename: José
authors.initials: J
authors.lastname: Borrell
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Vela
authors.forename: Angel
authors.initials: A
authors.lastname: Arévalo-Martin
authors.forename: Eduardo
authors.initials: E
authors.lastname: Molina-Holgado
authors.forename: Carmen
authors.initials: C
authors.lastname: Guaza
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D004731:Endotoxins / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics; D007109:Immunity / Q000187:drug effects*; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D011247:Pregnancy; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology*; D012559:Schizophrenia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D004731:Endotoxins; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone