Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice.
Epidemiological reports describe a strong association between prenatal human influenza viral infection and later development of schizophrenia. Postmodern human brain studies, however, indicate a lack of gliosis in schizophrenic brains presumably secondary to absence of glial cells during the second trimester viral infection in utero. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of glial fibrillary acidic protein (GFAP, an important marker of gliosis, neuron migration, and reactive injury) in developing brains of postnatal days 0, 14 and 35 mice. Determination of cellular GFAP immunoreactivity (IR) expressed as cell density in cortex and hippocampus of control and experimental brains showed increases in GFAP-positive density in exposed cortical (P = 0.03 day 14 vs control) and hippocampal cells (P = 0.035 day 14, P = 0.034 day 35). Similarly, ependymal cell layer GFAP-IR cell counts showed increases with increasing brain age from day 0, to days 14 and 35 in infected groups (P = 0.037, day 14) vs controls. The GFAP-positive cells in prenatally exposed brains showed 'hypertrophy' and more stellate morphology. These results implicate a significant role of prenatal human influenza viral infection on subsequent gliosis, which persists throughout brain development in mice from birth to adolescence.
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, MN, USA. fatem002@umn.edu
S H
SH
Fatemi
E S
ES
Emamian
R W
RW
Sidwell
D A
DA
Kist
J M
JM
Stary
J A
JA
Earle
P
P
Thuras
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000196:embryology*; D051379:Mice; D009474:Neurons / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D005904:Glial Fibrillary Acidic Protein