Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

Alboni, Silvia; Poggini, S.; Garofalo, Stefano; Milior, Giampaolo; Hajj, Hassan El; Lecours, Cynthia; Girard, Isabelle; Gagnon, Steven; Boisjoly-Villeneuve, Samuel; Brunello, Nicoletta; Wolfer, David P; Limatola, Cristina; Tremblay, Marie‐Ève; Maggi, Laura; Branchi, Igor

doi:10.1016/j.bbi.2016.07.155

Cited by 95 publications

(72 citation statements)

References 85 publications

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“…As a further consequence, SSRIs are expected to amplify the influence of living conditions on mood in a dose-dependent manner. Such hypothesis is supported by preclinical data 3, 4, 5 showing that fluoxetine treatment leads to an improvement of the depression-like phenotype when administered in an enriched condition, while it leads to a worsening when administered in a stressful condition. In addition, SSRI treatment consequences on selected end points, such as vulnerability to obesity, have been shown to be dependent on the quality of the environment.…”

Section: Introductionmentioning

confidence: 83%

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study

et al. 2017

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Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage −20 or 40 mg per day of citalopram. We found that sociodemographic characteristics affected treatment response in the same direction in the two dose groups, but these effects reached statistical significance only in the 40 mg per day dose group. In the latter, higher improvement rate was associated with having a working employment status (P=0.0219), longer education (P=0.0053), high income (P=0.01) or a private insurance (P=0.0031), and the higher remission rate was associated with having a working employment status (P=0.0326) or longer education (P=0.0484). Moreover, the magnitude of the effect of the sociodemographic characteristics on mood, measured as the percent of patients showing a positive outcome when exposed to favorable living conditions, was much greater—up to 37-fold—in the 40 compared to the 20 mg per day dose group. Overall, our results indicate that citalopram amplifies the influence of the living conditions on mood in a dose-dependent manner. These findings provide a potential explanation for the variable efficacy of SSRIs and might lead to the development of personalized strategies aimed at enhancing their efficacy.

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Section: Introductionmentioning

confidence: 83%

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study

et al. 2017

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“…Additionally, automated segmented axons were overlaid with the thresholded image, and axons that were missed by the automated segmentation were manually traced. The g ‐ratio was estimated by dividing the mean inner diameter by the mean outer diameter of axons in each distance bin . To verify the reasonableness of our estimation, axons were manually traced from one representative image from SW, PW, and sham group and obtained g ‐ratios of 0.46 ± 0.13 ( n = 1348), 0.56 ± 0.10 ( n = 1200), and 0.54 ± 0.08 ( n = 1605), respectively .…”

Section: Methodsmentioning

confidence: 99%

Soft Conducting Elastomer for Peripheral Nerve Interface

Zheng

Woeppel

Griffith

et al. 2019

Adv Healthcare Materials

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State‐of‐the‐art intraneural electrodes made from silicon or polyimide substrates have shown promise in selectively modulating efferent and afferent activity in the peripheral nervous system. However, when chronically implanted, these devices trigger a multiphase foreign body response ending in device encapsulation. The presence of encapsulation increases the distance between the electrode and the excitable tissue, which not only reduces the recordable signal amplitude but also requires increased current to activate nearby axons. Herein, this study reports a novel conducting polymer based intraneural electrode which has Young's moduli similar to that of nerve tissue. The study first describes material optimization of the soft wire conductive matrix and evaluates their mechanical and electrochemical properties. Second, the study demonstrates 3T3 cell survival when cultured with media eluted from the soft wires. Third, the study presents acute in vivo functionality for stimulation of peripheral nerves to evoke force and compound muscle action potential in a rat model. Furthermore, comprehensive histological analyses show that soft wires elicit significantly less scar tissue encapsulation, less changes to axon size, density and morphology, and reduced macrophage activation compared to polyimide implants in the sciatic nerves at 1 month postimplantation.

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“…This is of great interest as we have reported that fetal and neonatal exposure to fluoxetine increased the proportion of offspring with mild‐to‐moderate NASH (De Long et al, ). Moreover, as fluoxetine has been shown to increase production of IL1β (Alboni et al, ), which is mainly dependent on activation of the NLRP3 inflammasome (Martinon, Burns, & Tschopp, ), these data suggest that the increased prevalence of NASH in offspring born to fluoxetine‐exposed dams may be a result of dysregulated de novo lipogenesis and activation of the NLRP3 inflammasome. Hence, the present study was designed to investigate the effects of fetal and neonatal exposure to fluoxetine on the transcriptional and epigenetic regulation of genes involved in hepatic de novo lipid synthesis and the NLRP3 inflammasome.…”

Section: Introductionmentioning

confidence: 92%

Increased incidence of non‐alcoholic fatty liver disease in male rat offspring exposed to fluoxetine during fetal and neonatal life involves the NLRP3 inflammasome and augmented de novo hepatic lipogenesis

Long

Hardy

et al. 2017

J of Applied Toxicology

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Up to 10% of women take selective serotonin reuptake inhibitors (SSRI) during pregnancy. Children exposed to SSRIs in utero have an increased risk of being overweight suggesting that fetal exposure to SSRIs can cause permanent metabolic changes. We have previously shown in rats that fetal and neonatal exposure to the SSRI antidepressant fluoxetine results in metabolic perturbations including increased hepatic triglyceride content; a hallmark of non‐alcoholic fatty liver disease (NAFLD). Therefore, the aim of this study was to identify the mechanism(s) underlying the fluoxetine‐induced increase in intrahepatic triglyceride content. Female nulliparous Wistar rats were given vehicle or fluoxetine (10 mg/kg/day) orally for 2 weeks prior to mating until weaning. At 6 months of age, we assessed whether SSRI exposure altered components of the hepatic triglyceride biosynthesis pathway in the offspring and examined the molecular mechanisms underlying these changes. Male SSRI‐exposed offspring had a significant increase in the steady‐state mRNA levels of Elovl6 and Dgat1 and core components of the NLRP3 inflammasome (apoptosis‐associated speck‐like protein containing a caspase activation recruitment domain [ASC] and caspase‐1). Augmented expression of Asc in the SSRI‐exposed offspring coincided with increased histone acetylation in the proximal promoter region. Given that we have previously demonstrated that antenatal exposure to SSRIs can lead to fatty liver in the offspring, this raises concerns regarding the long‐term metabolic sequelae of fetal SSRI exposure. Moreover, this study suggests that elevated hepatic triglyceride levels observed in the SSRI‐exposed offspring may be due, in part, to activation of the NLRP3 inflammasome and augmentation of de novo lipogenesis.

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Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

Cited by 95 publications

References 85 publications

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study

Soft Conducting Elastomer for Peripheral Nerve Interface

Increased incidence of non‐alcoholic fatty liver disease in male rat offspring exposed to fluoxetine during fetal and neonatal life involves the NLRP3 inflammasome and augmented de novo hepatic lipogenesis

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