Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice
Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice
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DOI：
10.1038/sj.mp.4001046
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发表时间：
2002-01-01
影响因子：
11
通讯作者：
Thuras, P
中科院分区：
文献类型：
--
作者：
Fatemi, SH;Emamian, ES;Thuras, P
流行病学报告描述了产前人类流感病毒感染与后来的精神分裂症发展之间的密切联系：然而，后现代人类大脑研究表明，精神分裂症患者大脑中缺乏神经胶质细胞增生，这可能是由于子宫内妊娠中期病毒感染期间神经胶质细胞的缺乏所致。我们假设怀孕第 9 天的小鼠感染人类流感会改变出生后第 0、14 和 35 天小鼠发育中大脑中胶质纤维酸性蛋白（GFAP，胶质增生、神经元迁移和反应性损伤的重要标志物）的表达。细胞 GFAP 免疫反应性 (IR) 的测定以对照和实验大脑皮层和海马中的细胞密度表示，结果显示暴露的皮层（第 14 天与对照相比，P = 0.03）和海马细胞（第 14 天，P = 0.035，第 35 天，P = 0.034）中 GFAP 阳性密度增加。同样，与对照组相比，从第 0 天到第 14 天和第 35 天，感染组（P = 0.037，第 14 天）室管膜细胞层 GFAP-IR 细胞计数随着脑年龄的增加而增加。产前暴露的大脑中的 GFAP 阳性细胞表现出“肥大”和更多的星状形态。这些结果表明，产前人类流感病毒感染对随后的神经胶质增生具有重要作用，这种神经胶质增生在小鼠从出生到青春期的整个大脑发育过程中持续存在。
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.