PMID- 31955175 OWN - NLM STAT- MEDLINE DCOM- 20210203 LR - 20231012 IS - 1423-0313 (Electronic) IS - 0031-7012 (Linking) VI - 105 IP - 5-6 DP - 2020 TI - Scopoletin Activates Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling Pathway and Improves Functional Recovery after Spinal Cord Injury in Rats. PG - 349-359 LID - 10.1159/000503866 [doi] AB - BACKGROUND: Scopoletin (SPT) is known to exert neuroprotective autophagy effect. However, the efficacy of SPT in the treatment of spinal cord injury (SCI) has yet not been explored. The investigation was intended to elucidate whether SPT can exert neuroprotective effect by triggering neuronal autophagy after SCI. The study was also directed to investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in the autophagy facilitated by SPT. MATERIALS AND METHODS: The SCI was developed in female Sprague-Dawley rats by damaging the T10 spinal level using an impounder impact. Three animals groups were investigated - Sham group, SCI group, and SCI + SPT group. The SCI + SPT group was administered with SPT (100 mg/kg) intraperitoneally. Basso, Beattie, and Bresnahan scores and angle of incline test revealed that SPT administration improved the movement of hind limbs after SCI induction. RESULTS: Results indicated that SPT imparted neuronal protection, alleviated neuronal apoptosis, and improved neuronal autophagy. SPT-induced autophagy was identified by increased Beclin-1 expression and LC3B-positive neuronal cells. Further investigations revealed that SPT triggers the pathway involving AMPK/mTOR signaling, thereby stimulating autophagy in SCI-induced rat model. CONCLUSION: The findings of the present investigation strongly advocate the beneficial effects of SPT in the treatment of the SCI. SPT ameliorates the AMPK/mTOR signaling-induced autophagy and thereby improves functional recovery in SCI-induced rats. CI - (c) 2020 S. Karger AG, Basel. FAU - Zhou, Ruijuan AU - Zhou R AD - Department of Rehabilitation, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Kan, Shifeng AU - Kan S AD - Department of Rehabilitation, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Cai, Song AU - Cai S AD - Department of Rehabilitation, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Sun, Ran AU - Sun R AD - Department of Rehabilitation, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Yuan, Haixin AU - Yuan H AD - Department of Rehabilitation, Shanghai Fifth Rehabilitation Hospital, Shanghai, China. FAU - Yu, Bo AU - Yu B AD - Department of Rehabilitation, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China, blainedavidsonchu@yahoo.com. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20200117 PL - Switzerland TA - Pharmacology JT - Pharmacology JID - 0152016 RN - 0 (Neuroprotective Agents) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - KLF1HS0SXJ (Scopoletin) SB - IM RIN - Pharmacology. 2024;109(1):65. PMID: 37827136 MH - AMP-Activated Protein Kinases/*metabolism MH - Animals MH - Apoptosis/drug effects MH - Autophagy/drug effects MH - Female MH - Locomotion/drug effects MH - Neurons/drug effects MH - Neuroprotective Agents/*pharmacology/therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function/drug effects MH - Scopoletin/*pharmacology/therapeutic use MH - Signal Transduction/drug effects MH - Spinal Cord/drug effects MH - Spinal Cord Injuries/*drug therapy/metabolism/pathology/physiopathology MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - Autophagy OT - Neuroprotective OT - Scopoletin OT - Spinal cord injury EDAT- 2020/01/20 06:00 MHDA- 2021/02/04 06:00 CRDT- 2020/01/20 06:00 PHST- 2019/08/20 00:00 [received] PHST- 2019/10/01 00:00 [accepted] PHST- 2020/01/20 06:00 [pubmed] PHST- 2021/02/04 06:00 [medline] PHST- 2020/01/20 06:00 [entrez] AID - 000503866 [pii] AID - 10.1159/000503866 [doi] PST - ppublish SO - Pharmacology. 2020;105(5-6):349-359. doi: 10.1159/000503866. Epub 2020 Jan 17.