Effect of fluoxetine on the expression of tryptophan hydroxylase and 14-3-3 protein in the dorsal raphe nucleus and hippocampus of rat

Choi, Mi Ran; Hwang, Se Jin; Park, Geu Meum; Jung, Kyung Hwa; Kim, Seok Hyeon; Das, Nando Dulal; Chai, Young Gyu

doi:10.1016/j.jchemneu.2012.01.001

Cited by 14 publications

(8 citation statements)

References 48 publications

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“…The effects of chronic FLX on TPH immunoreactivity are indicative of a clear age-at-treatment dependence, with post-hoc tests showing higher TPH expression in adolescent-treated animals and a reduced expression in adult-treated rats. MacGillivray et al (2010)[32] reported reduced TPH expression in adult animals directly after acute or chronic FLX treatment, while others failed to see any effect after either 5 or 14 days of FLX treatment [71]. TPH mRNA expression was found to be increased in the DRN after 4 and 8 weeks of FLX treatment [7], but decreases were reported in the medial raphe nucleus, although this was after 2 weeks of treatment and with a much higher dose (i.e., 25 mg/kg vs. 7.5 mg/kg) [72].…”

Section: Discussionmentioning

confidence: 99%

Effects of Chronic Fluoxetine Treatment on Neurogenesis and Tryptophan Hydroxylase Expression in Adolescent and Adult Rats

et al. 2014

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The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

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Section: Discussionmentioning

confidence: 99%

Effects of Chronic Fluoxetine Treatment on Neurogenesis and Tryptophan Hydroxylase Expression in Adolescent and Adult Rats

et al. 2014

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“…Consistently with these results, a 6 month low dose (5 mg/kg/day) treatment with Fluoxetine in rats has been shown to reduce trabecular thickness and increase endocortical bone volume [54]. The dose of Fluoxetine tested by Branco-de-Almeida et al was on the high end of the doses commonly used to suppress serotonin production in rats [55,56], about twice as high as the maximum recommended human dose (MRHD) [54], and was based on a previous work highlighting its anti-inflammatory properties [57]. It is actually possible that this high dose of Fluoxetine may be activating alternative immunomodulatory or antiinflammatory pathways that are responsible for the authors’ observations and that are overcoming the effects on serotonin metabolism.…”

Section: The Wnt Connectionmentioning

confidence: 81%

“…Fluoxetine in particular proved to affect preosteoclast viability to a greater extent than other drugs of this class, and this could help explain its effect on periodontitis. Furthermore, it cannot be ruled out that at least part of the positive effects of Fluoxetine on periodontitis could be explained through its action on the central nervous system, where it has been shown that Fluoxetine can increase Tph expression [56,61]. Strikingly, Yadav et al showed that deletion of the brain stem specific Tryptophan Hydroxylase 2 (Tph2) isoform, lead to a reduction in bone mass in mice, apparently activating an alternative and opposite mechanism to the one mediating the effects of the gut Tph isoform [62].…”

Section: The Wnt Connectionmentioning

confidence: 99%

Serotonin: a novel bone mass controller may have implications for alveolar bone

Galli

Macaluso

Passeri

2013

J Negat Results BioMed

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As recent studies highlight the importance of alternative mechanisms in the control of bone turnover, new therapeutic approaches can be envisaged for bone diseases and periodontitis-induced bone loss. Recently, it has been shown that Fluoxetine and Venlafaxine, serotonin re-uptake inhibitors commonly used as antidepressants, can positively or negatively affect bone loss in rat models of induced periodontitis. Serotonin is a neurotransmitter that can be found within specific nuclei of the central nervous system, but can also be produced in the gut and be sequestered inside platelet granules. Although it is known to be mainly involved in the control of mood, sleep, and intestinal physiology, recent evidence has pointed at far reaching effects on bone metabolism, as a mediator of the effects of Lrp5, a membrane receptor commonly associated with Wnt canonical signaling and osteoblast differentiation. Deletion of Lrp5 in mice lead to increased expression of Tryptophan Hydroxylase 1, the gut isoform of the enzyme required for serotonin synthesis, thus increasing serum levels of serotonin. Serotonin, in turn, could bind to HTR1B receptors on osteoblasts and stop their proliferation by activating PKA and CREB.Although different groups have reported controversial results on the existence of an Lrp5-serotonin axis and the action of serotonin in bone remodeling, there is convincing evidence that serotonin modulators such as SSRIs can affect bone turnover. Consequently, the effects of this drug family on periodontal physiology should be thoroughly explored.

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“…While one study found no effects of haloperidol, olanzapine, lithium or a combination thereof on 14-3-3 expression levels in rat cortex or striatum (Dean et al, 2007), more recently subtle up-regulating effects of the mood stabilizers lithium and valproate on 14-3-3 levels in the PSD (Nanavati et al, 2011), as well as up-regulating effects of the SSRI antidepressant fluoxetine on 14-3-3-immunoreactivity in rat hippocampus have been reported (Choi et al, 2012). It is therefore possible that our proteomic findings were influenced by medication effects, although post-hoc analyses in the pH 4-7 study were negative (Focking et al, 2011a).…”

Section: -3-3 Signalingmentioning

confidence: 99%

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

Schubert¹,

Föcking²,

Cotter³

2015

Schizophrenia Research

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Effect of fluoxetine on the expression of tryptophan hydroxylase and 14-3-3 protein in the dorsal raphe nucleus and hippocampus of rat

Cited by 14 publications

References 48 publications

Effects of Chronic Fluoxetine Treatment on Neurogenesis and Tryptophan Hydroxylase Expression in Adolescent and Adult Rats

Effects of Chronic Fluoxetine Treatment on Neurogenesis and Tryptophan Hydroxylase Expression in Adolescent and Adult Rats

Serotonin: a novel bone mass controller may have implications for alveolar bone

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

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