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.
Long-lasting effects of neonatal dexamethasone treatment on spatial learning and hippocampal synaptic plasticity: involvement of the NMDA receptor complex / P.J. Kamphuis, F. Gardoni, A. Kamal, G. Croiset, J.M. Bakker, F. Cattabeni, W.H. Gispen, F. van Bel, M.M.G. Di Luca, V.M. Wiegant. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 17:8(2003), pp. 911-913.
|Titolo:||Long-lasting effects of neonatal dexamethasone treatment on spatial learning and hippocampal synaptic plasticity: involvement of the NMDA receptor complex|
GARDONI, FABRIZIO (Secondo)
DILUCA, MONICA MARIA GRAZIA (Penultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2003|
|Appare nelle tipologie:||01 - Articolo su periodico|