| First Author | Ren K | Year | 2021 |
| Journal | Br J Pharmacol | Volume | 178 |
| Issue | 18 | Pages | 3682-3695 |
| PubMed ID | 33908633 | Mgi Jnum | J:348111 |
| Mgi Id | MGI:7627195 | Doi | 10.1111/bph.15510 |
| Citation | Ren K, et al. (2021) Quercetin relieves D-amphetamine-induced manic-like behaviour through activating TREK-1 potassium channels in mice. Br J Pharmacol 178(18):3682-3695 |
| abstractText | BACKGROUND AND PURPOSE: Quercetin is a well-known plant flavonoid with neuroprotective properties. Earlier work suggested it may relieve psychiatric disorders, cognition deficits and memory dysfunction through anti-oxidant and/or radical scavenging mechanisms. In addition, quercetin modulated the physiological function of some ion channels. However, the detailed ionic mechanisms of the bioeffects of quercetin remain unknown. EXPERIMENTAL APPROACH: Effects of quercetin on neuronal activities in the prefrontal cortex (PFC) and its ionic mechanisms were analysed by calcium imaging using mice bearing a green fluorescent protein, calmodulin, and M13 fusion protein and patch clamp in acute brain slices from C57BL/6 J mice and in HEK 293 cells. The possible ionic mechanism of action of quercetin on D-amphetamine-induced manic-like effects in mice was explored with c-fos staining and the open field behaviour test. KEY RESULTS: Quercetin reduced calcium influx triggered by PFC pyramidal neuronal activity. This effect involved increasing the rheobase of neuronal firing through decreasing membrane resistance following quercetin treatment. Spadin, a blocker of TREK-1 potassium channels, also blocked the effect of quercetin on the membrane resistance and neuronal firing. Further, spadin blocked the neuroprotective effects of quercetin. The effects of quercetin on TREK-1 channels could be mimicked by GF109203X, a protein kinase C inhibitor. In vivo, injection of quercetin relieved the manic hyperlocomotion in mice, induced by D-amphetamine. This action was partly alleviated by spadin. CONCLUSION AND IMPLICATIONS: TREK-1 channels are a novel target for quercetin, by inhibiting PKC. This action could contribute to both the neuroprotective and anti-manic-like effects. |
