Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi

• DOI: 10.1152/ajpregu.90396.2008
• Publication Date: 2009-01-15T03:36:29Z
• Authors: Michelle E. Schober; Robert A. McKnight; Xing Yu; Christopher W. Ca...; Xingrao Ke; Robert H. Lane
• Keywords: Synaptogenesis; Intrauterine growth restriction; Synaptophysin; Placental insufficiency

Uteroplacental insufficiency (UPI), the major cause of intrauterine growth restriction (IUGR) in developed nations, predisposes to learning impairment. The underlying mechanism is unknown. Neuronal N-methyl-d-aspartate receptors (NMDARs) are critical for synaptogenesis and throughout life. We hypothesized that UPI-induced IUGR alters rat hippocampal NMDAR NR2A/NR2B subunit ratio and/or NR1 mRNA isoform expression synaptic density at day 21 (P21). To test this hypothesis, was induced by bilateral uterine artery ligation late-gestation Sprague-Dawley dam. At P21, protein were measured, as levels synaptophysin. Neuronal, synaptic, glial CA1, CA3, dentate gyrus (DG) assessed immunofluorescence. increased NR1-3a 1-3b both sexes. In P21 males, C2' decreased C2, NR2A, NR2A-to-NR2B ratio, whereas females, NR2B protein. associated with myelin basic protein-to-neuronal nuclei DG. conclude has sex-specific effects neither neuronal loss nor appears account changes subunits. Rather, it possible composition altered. Our results suggest apparent recovery hippocampus may be hyperexcitability. speculate plays an important role IUGR-associated cognitive