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Effects of neonatal dexamethasone treatment on hippocampal synaptic function
Author(s) -
Lin HsiaoJu,
Huang ChiungChun,
Hsu KueiSen
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20885
Subject(s) - long term potentiation , synaptic plasticity , hippocampal formation , neuroscience , glucocorticoid , dexamethasone , hippocampus , stimulation , medicine , long term depression , neuroplasticity , psychology , endocrinology , glutamate receptor , ampa receptor , receptor
Objective Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Surprisingly, little is known about the long‐term neurodevelopmental outcomes of this therapy. Methods Using a schedule of tapering doses of DEX similar to that used in premature infants, we examined the consequences of neonatal DEX treatment on hippocampal synaptic plasticity of infants and associative memory later in their lives. Results Neonatal DEX treatment changed the direction of synaptic plasticity, favoring low‐frequency, stimulation‐induced, long‐term depression and opposing the induction of long‐term potentiation by high‐frequency stimulation in adolescent (5‐week‐old) rats, but these alterations disappeared in young adult (8‐week‐old) rats. The effects of DEX on long‐term depression and long‐term potentiation were found to correlate with an increase in the autophosphorylation of Ca 2+ /calmodulin‐dependent protein kinase II and a decrease in the protein phosphatase 1 activity. Neonatal DEX treatment also disrupted memory retention in 5‐week‐old (but not 8‐week‐old) rats subjected to passive avoidance learning tasks. Interpretation: These results suggest that neonatal DEX treatment alters hippocampal synaptic plasticity and contextual fear memory formation in later life, but these impairments apparently are not permanent. Ann Neurol 2006;59:939‐951