title: Expression of early growth response 1 affects miR-106a/signal transducer and activator of transcription 3 regulating cognitive impairment in ovariectomized mice.
abstract: 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.
authors.affiliation: From the 1State Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University; and 2Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cong
authors.forename: Chaojun
authors.initials: C
authors.lastname: Wang
authors.forename: Danhua
authors.initials: D
authors.lastname: Pu
authors.forename: Jiayin
authors.initials: J
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry; D003071:Cognition; D003072:Cognition Disorders / Q000503:physiopathology*; D051766:Early Growth Response Protein 1 / Q000032:analysis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D010052:Ovariectomy; D017698:Postmenopause / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D014162:Transfection
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse