Prenatal viral infection causes alterations in nNOS expression in developing mouse brains.
Epidemiological evidence points to prenatal viral infection being responsible for some forms of schizophrenia and autism. We hypothesized that prenatal human influenza viral infection in day 9 pregnant mice may cause changes in the levels of neuronal nitric oxide synthase (nNOS), an important molecule involved in synaptogenesis and excitotoxicity, in neonatal brains. Brains from 35- and 56-day-old mice were prepared for SDS-gel electrophoresis and Western blotting using polyclonal anti nNOS antibody. Quantification of nNOS showed time and region-dependent changes in the levels of nNOS protein. Mean rostral brain area value from prenatally infected animals showed a significant (p=0.067) increase of 147% in nNOS levels at 35 days postnatally, with an eventual 29% decrease on day 56. Middle and caudal brain areas showed reductions in nNOS in experimental mice at 35 and 56 days, with a significant 27% decrease in nNOS in the middle segment of day 56 brains (p=0.016). Significant interactions were found between group membership and brain area (Wilks lambda=0.440, F(2.9)=5.72, p=0.025); there was also a significant 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 the notion that prenatal viral infection affects brain development adversely via the pathological involvement of nNOS expression.
Fatemi
S H
SH
Department of Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA.
Cuadra
A E
AE
El-Fakahany
E E
EE
Sidwell
R W
RW
Thuras
P
P
D000818:Animals; D001321:Autistic Disorder / Q000821:virology; D001921:Brain / Q000196:embryology* / Q000201:enzymology*; D018792:Encephalitis, Viral / Q000201:enzymology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009976:Orthomyxoviridae Infections / Q000201:enzymology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012559:Schizophrenia / Q000821:virology; D013047:Specific Pathogen-Free Organisms
D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse