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Quercetin Relieves D-Amphetamine induced Manic-like Behavior through Activating TREK-1 Potassium Channels in Mice
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  • Keke Ren,
  • Baolin Guo,
  • Rui Li,
  • Honghui Mao,
  • Han Yao,
  • Shenxi Wu,
  • Zhantao Bai,
  • Wenting Wang
Keke Ren
Fourth Military Medical University
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Baolin Guo
Fourth Military Medical University
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Rui Li
Fourth Military Medical University
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Honghui Mao
Fourth Military Medical University
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Han Yao
Fourth Military Medical University
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Shenxi Wu
Fourth Military Medical University
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Zhantao Bai
Yan'an University
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Wenting Wang
Fourth Military Medical University
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Abstract

Background and Purpose: Quercetin is a prominent neuroprotective compound from flavonoids. Previous studies found it may relieve psychiatric disorders, cognition deficits, and memory dysfunction through anti-oxidation and/or radical scavenging mechanisms. In addition, Quercetin also was found to modulate the physiological function of a few types of ion channels. However, the detailed ionic mechanisms of quercetin’s bioeffect remain unknown. Experimental Approach: We examined the effect neuronal activities changes in prefrontal cortex (PFC) and its ionic mechanisms upon quercetin application by using GCaMP calcium imaging and patch clamp in acute brain slices. Then we explored the potential ionic mechanism of quercetin on D-amphetamine induced manic-like using c-fos staining and the open field behavior test. Key Results: Quercetin reduced calcium influx triggered by PFC pyramidal neuronal activity. This effect was caused by increasing the rheobase of neuronal firing through decreasing membrane resistance upon quercetin treatment. Spadin, a TREK-1 potassium channel (a two-pore-domain background potassium channel) inhibitor, could block the effect of quercetin on the membrane resistance and neuronal firing. And also, Spadin can block the neural protective effects of quercetin. In addtion, intraperitoneal injection of quercetin could relieve the manic hyperlocomotion of the mice induced by D-amphetamine, which can be partially alleviated by Spadin. Conclusion and Implications: Our results demonstrated that TREK-1 channel is a novel target on quercetin treatment, which could contribute to both the neuroprotection and anti-manic-like effects.

Peer review status:ACCEPTED

13 Jun 2020Submitted to British Journal of Pharmacology
15 Jun 2020Submission Checks Completed
15 Jun 2020Assigned to Editor
19 Jun 2020Reviewer(s) Assigned
07 Sep 2020Review(s) Completed, Editorial Evaluation Pending
15 Sep 2020Editorial Decision: Revise Minor
15 Jan 20211st Revision Received
17 Jan 2021Submission Checks Completed
17 Jan 2021Assigned to Editor
20 Jan 2021Reviewer(s) Assigned
31 Jan 2021Review(s) Completed, Editorial Evaluation Pending
05 Feb 2021Editorial Decision: Revise Minor
05 Apr 20212nd Revision Received
07 Apr 2021Submission Checks Completed
07 Apr 2021Assigned to Editor
09 Apr 2021Editorial Decision: Accept