Background: Epidemiological studies have indicated that maternal infection during pregnancy may lead to a\r\nhigher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune\r\nresponse, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C)\r\ntreatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in\r\nhumans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia.\r\nMethods: We examined whether suppression of the maternal immune response could prevent\r\nneurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic\r\nmaternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-a) and\r\ninterleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-B inhibitor\r\npyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental\r\ndisorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance\r\ntests.\r\nResults: PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive\r\nincreases in serum TNF-a and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive\r\navoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and\r\nreduced the severity of neurodevelopmental defects in adult offspring.\r\nConclusions: Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and\r\npartially prevent neurodevelopmental disorders of adult offspring.
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