4.7 Article

Fluoxetine increases astrocytic glucose uptake and glycolysis in corticosterone-induced depression through restricting GR-TXNIP-GLUT1 Pathway

期刊

FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.872375

关键词

fluoxetine; astrocyte; glycolysis; GR; TXNIP-GLUT1 pathway

资金

  1. National Natural Science Foundation of P. R. China
  2. National Key R&D Program of China
  3. Open Project of State Key Laboratory of Natural Medicines
  4. [81773929]
  5. [82174000]
  6. [2019YFC1711000]
  7. [SKLNMKF202204]

向作者/读者索取更多资源

Fluoxetine improves glucose uptake and glycolysis in astrocytes by restricting the GR-TXNIP-GLUT1 pathway, thereby alleviating corticosterone-induced depression.
Antidepressant fluoxetine can affect cerebral glucose metabolism in clinic, but the underlying molecular mechanism remains poorly understood. Here, we examined the effect of fluoxetine on brain regional glucose metabolism in a rat model of depression induced by repeated corticosterone injection, and explored the molecular mechanism. Fluoxetine was found to recover the decrease of F-18-fluorodeoxyglucose (F-18-FDG) signal in prefrontal cortex (PFC), and increased 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG, a fluorescent glucose analog) uptake in an astrocyte-specific manner in ex vivo cultured PFC slices from corticosterone-induced depressive rats, which were consistent with its improvement of animal depressive behaviors. Furthermore, fluoxetine restricted nuclear translocation of glucocorticoid receptor (GR) to suppress the transcription of thioredoxin interacting protein (TXNIP). Subsequently, it promoted glucose transporter 1 (GLUT1)-mediated glucose uptake and glycolysis of PFC astrocytes through suppressing TXNIP expression under corticosterone-induced depressive state. More importantly, fluoxetine could improve glucose metabolism of corticosterone-stimulated astrocytes via TXNIP-GLUT1 pathway. These results demonstrated that fluoxetine increased astrocytic glucose uptake and glycolysis in corticosterone-induced depression via restricting GR-TXNIP-GLUT1 pathway. The modulation of astrocytic glucose metabolism by fluoxetine was suggested as a novel mechanism of its antidepressant action.

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