Prenatal viral infection has been associated with the development of
schizophrenia and
autism. Our laboratory has previously shown that
viral infection causes deleterious effects on
brain structure and function in
mouse offspring following late
first trimester (E9) and late
second trimester (E18) administration of
influenza virus. We hypothesized that middle
second trimester infection (E16) in
mice may lead to a different pattern of
brain gene expression and structural defects in the developing offspring. C57BL6
mice were infected on E16 with a sublethal dose of
human influenza virus or sham-infected using vehicle
solution. Male offspring of the infected
mice were collected at P0, P14, P35, and P56, their
brains removed and cerebella
dissected and
flash frozen.
Microarray, DTI and
MRI scanning, as well as qRT-PCR and
SDS-PAGE and
western blotting analyses were performed to detect differences in
gene expression and
brain atrophy. Expression of several genes associated with
myelination, including Mbp, Mag, and Plp1 were found to be altered, as were protein levels of Mbp, Mag, and DM20.
Brain imaging revealed significant
atrophy in
cerebellum at P14, reduced fractional
anisotropy in
white matter of the right
internal capsule at P0, and increased fractional
anisotropy in
white matter in
corpus callosum at P14 and right
middle cerebellar peduncle at P56. We propose that maternal
infection in
mouse impacts
myelination genes.
