Prenatal viral infection causes alterations in nNOS expression in developing mouse brains

Epidemiological evidence points to prenatal viral infection being responsib le for some forms of schizophrenia and autism. We hypothesized that prenata l human influenza viral infection in day 9 pregnant mice may cause changes in the levels of neuronal nitric oxide synthase (nNOS), an important molecu le involved in synaptogenesis and excitotoxicity, in neonatal brains. Brain s from 35- and 56-day-old mice were prepared for SDS-gel electrophoresis an d Western blotting using polyclonal anti nNOS antibody. Quantification of n NOS showed time and region-dependent changes in the levels of nNOS protein. Mean rostral brain area value from prenatally infected animals showed a si gnificant (p = 0.067) increase of 147% in nNOS levels at 35 days postnatall y, with an eventual 29% decrease on day 56. Middle and caudal brain areas s howed reductions in nNOS in experimental mice at 35 and 56 days, with a sig nificant 27% decrease in nNOS in the middle segment of day 56 brains (p = 0 .016). Significant interactions were found between group membership and bra in area (Wilks lambda = 0.440, F(2.9)= 5.72, p = 0.025); there was also a s ignificant interaction between brain area, group and age (Wilks lambda = 0. 437, F(2.9) = 5.79, P = 0.024). These results provide further support for t he notion that prenatal viral infection affects brain development adversely via the pathological involvement of nNOS expression. NeuroReport 11:1493-1 496 (C) 2000 Lippincott Williams & Wilkins.