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Regulation of N-Methyl-D-Aspartate Receptor Subunit Expression in the Fetal Guinea Pig Brain¹

Departments of Physiology,³ Obstetrics and Gynecology,⁴ Medicine,⁵ Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

N-methyl-D-aspartate receptors (NMDARs) are critical for neuronal maturation and synaptic formation as well as for the onset of long-term potentiation, a process critical to learning and memory in postnatal life. In the current study, we demonstrated that NMDAR subunits undergo spatial, temporal, and sex-specific regulation. During development, we observed increasing NR1 and NR2A expression at the same time as levels of NR2B subunits decreased in the hippocampus and cortex in the fetal guinea pig. We have also shown that glucocorticoids can modulate fetal NMDAR subunit expression in a sex-specific fashion. This is clinically important because synthetic glucocorticoids are administered to pregnant women at risk of preterm labor. Repeated exposure to exogenous glucocorticoids caused a dose-dependent decrease in NR1 mRNA levels and increased NR2A mRNA expression in the female hippocampus at Gestational Day 62. There are significant changes in NMDAR subunit expression in late gestation. It is possible that these alter NMDA-dependent signaling at this time. Prenatal exposure to exogenous glucocorticoids modifies the trajectory of NMDAR subunit expression in females but not in males.

¹ Supported by the Canadian Institute for Health Research (CIHR) Premier Research Excellence Award (PREA) to S.G.M. (MOP-49511), and a CIHR MD/PhD Studentship to D.O.

² Correspondence: S.G. Matthews, Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. FAX: 416 978 4940; stephen.matthews{at}utoronto.ca

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