title: Dexamethasone administration to the neonatal rat results in neurological dysfunction at the juvenile stage even at low doses.
abstract: Dexamethasone (DEX), a synthetic glucocorticoid, has been widely used to prevent the development of a variety of poor health conditions in premature infants including chronic lung disease, inflammation, circulatory failure, and shock. Although there are some reports of neurologic complications related to DEX exposure, its full effects on the premature brain have not been examined in detail. To investigate the effects of DEX on neural development, we first administered low doses (0.2 mg/kg bodyweight or less) of the glucocorticoid to neonatal rats on a daily basis during the first postnatal week and examined subsequent behavioral alterations at the juvenile stage. DEX-treated rats exhibited not only a significant reduction in both somatic and brain weights but also learning disabilities as revealed in the shuttle avoidance test. The hippocampi of DEX-treated rats displayed a high apoptotic and a low mitotic cell density compared to control rats on day 7 after birth. In a subsequent experiment, neural stem/progenitor cells were cultured in the presence of DEX for 6 days. The glucocorticoid inhibited cell growth without an increase in cell death. These results suggest that administration of DEX to premature infants induces neurological dysfunction via inhibition of the proliferation of neural stem/progenitor cells.
authors.affiliation: Division of Obstetrics and Gynecology, Aichi Medical University Graduate School of Medicine, Nagakute, Aichi 480-1195, Japan. yukoichi@poem.ocn.ne.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ichinohashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Miharu
authors.initials: M
authors.lastname: Ito
authors.forename: Kimi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wakatsuki
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Oohira
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology*; D058953:Neural Stem Cells / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects*; D051381:Rats; D014741:Video Recording
chemical_list: D003907:Dexamethasone