Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia.
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.
Borrell
José
J
Psychobiology Group, Neural Plasticity Department, Cajal Institute, 28002, Madrid, Spain. cgjb@cajal.csic.es
Vela
José Miguel
JM
Arévalo-Martin
Angel
A
Molina-Holgado
Eduardo
E
Guaza
Carmen
C
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
D014150:Antipsychotic Agents; D004731:Endotoxins; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone