RRC ID 34767
Author Mendez-David I, Tritschler L, Ali ZE, Damiens MH, Pallardy M, David DJ, Kerdine-Römer S, Gardier AM.
Title Nrf2-signaling and BDNF: A new target for the antidepressant-like activity of chronic fluoxetine treatment in a mouse model of anxiety/depression.
Journal Neurosci Lett
Abstract Several studies have shown that Nrf2, a major redox-sensitive transcription factor involved in the cellular defense against oxidative stress, increases susceptibility to depressive-like behavior. However, little is known about the influence of antidepressant drugs on Nrf2 signaling and expression of its target genes (GCLC, NQO1, HO-1) in the brain. We found that chronic treatment of a mouse model of anxiety/depression (CORT model) with a selective serotonin reuptake inhibitor (SSRI, fluoxetine, 18mg/kg/day) reversed CORT-induced anxiety/depression-like behavior in mice. Chronic fluoxetine treatment restored CORT-induced decreases in Nrf2 protein levels and its target genes in the cortex and hippocampus. Furthermore, we found that chronic fluoxetine also increased brain derived neurotrophic factor (BDNF) protein levels in cortex and hippocampus of CORT-treated Nrf2 knockout mice (KO, Nrf2(-/-)). Taken together, these data suggest that Nrf2 signaling contributes to fluoxetine-induced neuroprotection via an unexpected mechanism involving 5-HT transporter SERT blockade, and not through enhancement of BDNF expression.
Volume 597
Pages 121-6
Published 2015-6-15
DOI 10.1016/j.neulet.2015.04.036
PII S0304-3940(15)00335-3
PMID 25916883
MeSH Animals Antidepressive Agents / pharmacology* Antidepressive Agents / therapeutic use Anxiety / drug therapy* Anxiety / metabolism Brain-Derived Neurotrophic Factor / metabolism* Cerebral Cortex / drug effects Cerebral Cortex / metabolism Corticosterone / pharmacology Depression / drug therapy* Depression / metabolism Fluoxetine / pharmacology* Fluoxetine / therapeutic use Hippocampus / drug effects Hippocampus / metabolism Male Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 / genetics NF-E2-Related Factor 2 / metabolism* Signal Transduction
IF 2.274
Times Cited 45
Mice RBRC01390