Faculty Collaboration Database

Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi. Am J Physiol Regul Integr Comp Physiol 2009 Mar;296(3):R681-92

Date

01/16/2009

Pubmed ID

19144756

DOI

10.1152/ajpregu.90396.2008

Scopus ID

2-s2.0-64149090673 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

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

Author List

Schober ME, McKnight RA, Yu X, Callaway CW, Ke X, Lane RH

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Brain
Brain Chemistry
Female
Fetal Growth Retardation
Fluorescent Antibody Technique
Glial Fibrillary Acidic Protein
Hippocampus
Immunohistochemistry
Male
Placental Circulation
Placental Insufficiency
Pregnancy
RNA
Rats
Receptors, N-Methyl-D-Aspartate
Uterus