title: Long-lasting effects of neonatal dexamethasone treatment on spatial learning and hippocampal synaptic plasticity: involvement of the NMDA receptor complex.
abstract: The effects of neonatal dexamethasone (DEX) treatment on spatial learning and hippocampal synaptic plasticity were investigated in adult rats. Spatial learning in reference and working memory versions of the Morris maze was impaired in DEX-treated rats. In hippocampal slices of DEX rats, long-term depression was facilitated and potentiation was impaired. Paired-pulse facilitation was normal, suggesting a postsynaptic defect as cause of the learning and plasticity deficits. Western blot analysis of hippocampal postsynaptic densities (PSD) revealed a reduction in NR2B subunit protein, whereas the abundance of the other major N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A), AMPA receptor subunits (GluR2/3), scaffolding proteins, and Ca2+/calmodulin-dependent protein kinase II (alphaCaMKII) were unaltered. This selective reduction in NR2B likely resulted from altered receptor assembly rather than subunit expression, because the abundance of NR2B in the homogenate and crude synaptosomal fractions was unaltered. In addition, the activity of alphaCaMKII, an NMDA receptor complex associated protein kinase, was increased in PSD of DEX rats. The results indicate that neonatal treatment with DEX causes alterations in composition and function of the hippocampal NMDA receptor complex that persist into adulthood. These alterations likely explain the deficits in hippocampal synaptic plasticity and spatial learning induced by neonatal DEX treatment.
authors.affiliation: Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Patrick J G H
authors.initials: PJ
authors.lastname: Kamphuis
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Amer
authors.initials: A
authors.lastname: Kamal
authors.forename: Gerda
authors.initials: G
authors.lastname: Croiset
authors.forename: Joost M
authors.initials: JM
authors.lastname: Bakker
authors.forename: Flaminio
authors.initials: F
authors.lastname: Cattabeni
authors.forename: Willem Hendrik
authors.initials: WH
authors.lastname: Gispen
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.forename: Victor M
authors.initials: VM
authors.lastname: Wiegant
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013037:Spatial Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D005938:Glucocorticoids; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D003907:Dexamethasone; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases