Quercetin Relieves D-Amphetamine induced Manic-like Behavior through Activating TREK-1 Potassium Channels in Mice.

Please login or register to bookmark this article
Bookmark this %label%

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 scavengingmechanisms. 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.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 and HEK 293 cells. Then we explored the potential ionic mechanism of quercetin on D-amphetamine induced manic-like effects using c-fos staining and the open field behavior test.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. Moreover, the effect of quercetin on TREK-1 channel could be mimicked by GF109203X, a protein kinase C inhibitor. 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.Our results demonstrated that TREK-1 channel is a novel target on quercetin treatment through PKC-dependent manner, which could contribute to both the neuroprotection and anti-manic-like effects.

View the full article @ British journal of pharmacology
Get PDF with LibKey

Authors: Keke Ren, Haiying Liu, Baolin Guo, Rui Li, Honghui Mao, Qian Xue, Han Yao, Shengxi Wu, Zhantao Bai, Wenting Wang