Nrf2-signaling and BDNF: A new target for the antidepressant-like activity of chronic fluoxetine treatment in a mouse model of anxiety/depression

BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia

“…The efficacy of antidepressants to decrease oxidative stress via activation of Nrf2 signaling has been previously noted (Martín-de-Saavedra et al, 2013; Mendez-David et al, 2015; Uchihara et al, 2016; Yao et al, 2016; Zhang et al, 2013), leading to the hypothesis that oxidative stress contributes to the pathogenesis of depressive disorders (Mendez-David et al, 2015; Lee et al, 2013). Although our results show shorter immobility time, and thus less depression-like behavior in the BXD21/TyJ RI strain (considered high Nrf2 expressing at PND 21) (Fig.…”

“…Other studies have used growth factors and cytokines as biomarkers for diagnosis of several psychiatric disorders, focusing on the role of growth factors and their relationship to anxiety-related behaviors (cognitive, emotional and social) (Galvez-Contreras et al, 2016). Furthermore, the potential anti-inflammatory properties of Nrf2 have emerged as a promising approach for neuroprotection in the face of depression and anxiety disorders (Martín-de-Saavedra et al, 2013; Muramatsu et al, 2013; Zhang et al, 2013; Khalifeh et al, 2015; Mendez-David et al, 2015). In male mice, the effects of anxiety/depression have been reversed by fluoxetine, a selective serotonin reuptake inhibitor (SSRI), directly in response to the activation of Nrf2 signaling, both in the cortex and hippocampus (Mendez-David et al, 2015).…”

“…Furthermore, the potential anti-inflammatory properties of Nrf2 have emerged as a promising approach for neuroprotection in the face of depression and anxiety disorders (Martín-de-Saavedra et al, 2013; Muramatsu et al, 2013; Zhang et al, 2013; Khalifeh et al, 2015; Mendez-David et al, 2015). In male mice, the effects of anxiety/depression have been reversed by fluoxetine, a selective serotonin reuptake inhibitor (SSRI), directly in response to the activation of Nrf2 signaling, both in the cortex and hippocampus (Mendez-David et al, 2015). Consistent with these observations, Martín-de-Saavedra and collaborators (2013) identified Nrf2 as a target for the development of novel antidepressive drugs.…”

CDK5 knockdown in astrocytes provide neuroprotection as a trophic source via Rac1

“…Nfr2 and trophic factors (BDNF, GDNF, VEGF, NGF) show neuroprotection effects (Kam et al, 2011;Sakata et al, 2012), however the specific mechanism involving the ability of Nrf2 and BDNF to protect remains unclear. Approximations using Nrf2 knockout mice show that Nfr2 deficiency decreases BDNF levels (Mendez-David et al, 2015). Also, in C6 cells that produce BDNF and GDNF in a neuroprotection context, apparently, overexpression of dominant-negative Nrf2 mainly affects GDNF, showing that this molecule is a major trophic factor susceptible to Nfr2 (Hirata et al, 2012).…”

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

“…In humans, brain BDNF levels have been found to be reduced in postmortem samples from depressed patients, and antidepressant therapies restored brain BDNF level to the normal range (Matrisciano et al, 2009). As well as clinical studies, it has also been shown that BDNF expression was decreased in the hippocampus and prefrontal cortex of depressive animals, which could be reversed by long term antidepressant treatment (Mendez-David et al, 2015;Sahin et al, 2015). Therefore, when we examined the effects of red wine extract on the corticosterone-mediated decrease in BDNF protein levels, the results of long-term red wine extract treatment reversing the reduction suggested that the behavioral improvement in the model may be concurrent with increased BDNF levels.…”