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: Jing Cong, Chaojun Wang, Danhua Pu, Jiayin Liu, Gang Hu, Chao Gao, Jie Wu
• Journal: Menopause (New York, N.Y.) (Menopause) Vol. 21 Issue 10 Pg. 1143-50 (Oct 2014) ISSN: 1530-0374 [Electronic] United States
• PMID: 24686449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Early Growth Response Protein 1
• Egr1 protein, mouse
• MicroRNAs
• Mirn106 microRNA, mouse
• RNA, Messenger
• STAT3 Transcription Factor
• Stat3 protein, mouse

Topics

• Animals
• Cerebral Cortex (chemistry)
• Cognition
• Cognition Disorders (physiopathology)
• Early Growth Response Protein 1 (analysis, genetics)
• Female
• Gene Expression
• Hippocampus (chemistry)
• Humans
• Mice
• Mice, Inbred ICR
• MicroRNAs (analysis, genetics, physiology)
• Ovariectomy
• Postmenopause (physiology)
• RNA, Messenger (analysis)
• STAT3 Transcription Factor (analysis, genetics, physiology)
• Transfection