Objective: This study aims to investigate the effects of early growth response 1 (Egr1) on miR-106a/signal transducer and activator of transcription 3 (STAT3) regulating cognitive impairment in an ovariectomy model.
Methods: Using the Morris water maze test, we assessed escape latency and time spent in a quadrant among mice at 6, 8, and 12 weeks after ovariectomy and their age-matched controls (n = 15 each group). Egr1, miR-106a, and STAT3 messenger RNA expression (n = 7) in the hippocampus and cortex of mice at 6, 8, and 12 weeks after ovariectomy was detected by quantitative real-time polymerase chain reaction, whereas Egr1, phospho-STAT3 (p-STAT3), and STAT3 protein expression (n = 8) was evaluated by Western blot analysis. Moreover, alterations in miR-106a and STAT3 expression were investigated in neuroblastoma (SH-SY5Y) cells transfected with a human Egr1 interference fragment (si-Egr1) or an Egr1-overexpressing plasmid (GV141-Egr1), respectively.
Results: Escape latency was significantly increased and time spent in a platform quadrant was reduced in mice at 12 weeks after ovariectomy compared with age-matched controls. Egr1 and miR-106a expression was obviously increased in the hippocampus and cortex at 12 weeks after ovariectomy, whereas STAT3 levels were decreased compared with 12-week controls. After SH-SY5Y cell transfection with the si-Egr1 fragment, miR-106a levels decreased and STAT3/p-STAT3 levels increased, whereas cotransfection of the miR-106a mimic caused a significant decrease in STAT3 levels. MiR-106a messenger RNA expression was significantly increased and STAT3/p-STAT3 protein levels were decreased by Egr1 overexpression, whereas simultaneous transfection with the miR-106a inhibitor inhibited alterations in STAT3 levels.
Conclusions: This study suggests that Egr1 decreases STAT3 expression via miR-106a in ovariectomized mice with cognitive impairment, indicating that Egr1 represents a potential target for therapeutic intervention in postmenopausal cognitive decline.
(C) 2014 by The North American Menopause Society.