Abstract
OBJECTIVE: To model glucocorticoid-induced cognitive impairment and evaluate the neuroprotection by schizandrin (Sch) against dexamethasone (Dex)-induced neurotoxicity in vivo and in vitro. METHODS: Cerebral cortical cells from neonatal Sprague-Dawley rats (within 24 hours after birth) were cultured for 9 days, and then treated with Dex (10(-4), 10(-5), 10(-6) or 10(-7) mol/L) for 24 h or pretreated with 10(-4) mol/L Dex for 24 h followed by 10, 20, 40, or 80 μmol/L Sch for 48 h. Cell viability was assessed using the MTT assay. Immunofluorescence and real-time PCR for MAP2 were performed to confirm the effects of Dex on neurite outgrowth. In vivo, kunming mice were randomly divided into six groups: control [(intragastric (i.g.) vehicle for 42 days]; Dex group I (5 mg/kg · d(-1) Dex i.g. treatment for 28 days followed by i.g. vehicle for 14 days); Dex group II (Dex i.g. for 42 days); Dex + Sch (Dex i.g. for 28 days followed by 5, 15, or 45 mg/kg · d(-1) Sch i.g. for 14 days). Learning and memory were assessed by Morris water maze test. Histological examination was used to assess pathology and apoptosis in neurons. RESULTS: Compared to the Dex groups, Sch increased cell viability in a dose-dependent manner, improved performance in the Morris water maze and ameliorated the morphological changes. CONCLUSION: Sch has neuroprotective effects against insults induced by glucocorticoid.