Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

Conboy, Lisa; Varea, Emilio; Castro, Jorge; Sakouhi-Ouertatani, Hajer; Calandra, Thierry; Lashuel, Hilal A.; Sandi, Carmen

doi:10.1038/mp.2010.15

Cited by 85 publications

(99 citation statements)

References 72 publications

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“…Although reduced neurogenesis and depression-like phenotypes arise in tandem following various chronic stressors (e.g., Surget et al, 2008;Bessa et al, 2009a), a requirement for reduced neurogenesis in the development of a depression-like phenotype has apparently been demonstrated only by Conboy et al (2011). In our hands, however, cD2 KO mice, devoid of adult brain neurogenesis, did not show increased immobility in FST and TST tests.…”

Section: Discussioncontrasting

confidence: 41%

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

Jedynak

Kos

Sandi

et al. 2014

Journal of Psychiatric Research

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a b s t r a c tThe neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

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Section: Discussioncontrasting

confidence: 41%

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

Jedynak

Kos

Sandi

et al. 2014

Journal of Psychiatric Research

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“…Neuronal proliferation induced by fluoxetine can be blocked by MIF inhibition and MIF knockout [78] , which suggests that MIF plays a role in the neurogenesis induced by antidepressants. Further studies have shown that the MIF-mediated cell proliferation is mediated by BDNF.…”

Section: The Hypothalamus-pituitary-adrenal Axis Hyperactivity Hypothmentioning

confidence: 96%

“…After treatment with antidepressants, the infl ammatory levels in the peripheral circulation as well as MIF expression levels in macrophages and lymphocytes are reduced [77] . Although MIF expressed by infl ammatory cells (such as macrophages) in the peripheral circulation can act against glucocorticoids and infl ammation, inhibition of MIF cannot stop depression; instead, it induces anxiety-and depression-like phenotypes in laboratory animals, leading to a decline in hippocampus-dependent learning and memory [78] . This indicates that high levels of MIF expressed by leukocytes in the peripheral circulation can facilitate the development of depression, and MIF expressed in the CNS is essential for neurogenesis, mood regulation, as well as learning and memory, which is contradictory to its role in infl ammatory cells of the peripheral circulation.…”

Section: The Hypothalamus-pituitary-adrenal Axis Hyperactivity Hypothmentioning

confidence: 99%

New hypothesis and treatment targets of depression: an integrated view of key findings

2015

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Major depressive disorder (MDD) is a common and devastating psychiatric disorder characterized by persistent low mood, cognitive disorder, and impaired social function. Despite its complex mechanisms, increasing evidence has identified the involvement of neurotrophic factors, inflammatory cytokines, the hypothalamuspituitary-adrenal axis, and glutamate receptors in the pathophysiology of this illness. The present review synthesizes recent research achievements to defi ne the network between different hypotheses of MDD and to understand which part is most pivotal for its pathogenesis. By integrating MDD-related signal pathways, we highlight brain-derived neurotrophic factor (BDNF) dysfunction and increased apoptosis as the fi nal common cascades, and new therapeutic strategies aiming to enhance BDNF function have been shown to exert a rapid and effective antidepressant action.

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“…Both depression and PAH are characterized by increased levels of proinfl ammatory cytokines, such as interleukin-6 and tumor necrosis factor-a , which could refl ect a mechanistic link between these two disease processes. [33][34][35] These fi ndings are provocative, but whether there is a causal relationship between depression and the progression of PAH cannot be determined based on the present results. Alternatively, alleviation of depression could have a benefi cial effect on outcomes in PAH that is independent of any impact on pathogenic mechanisms; however, we were not able to evaluate any effect of SSRIs on depression in the present study.…”

Section: Unadjusted Outcomes: Mortality and Composite End Pointmentioning

confidence: 41%

Use of Selective Serotonin Reuptake Inhibitors and Outcomes in Pulmonary Arterial Hypertension

Sadoughi¹,

Roberts²,

Preston³

et al. 2010

Chest

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531T he serotonin hypothesis of pulmonary arterial hypertension (PAH) emerged . 40 years ago and was reemphasized in the 1990s following the association of pulmonary hypertension (PH) 1 with anorexic agents such as aminorex fumarate and fenfl uramine. [2][3][4][5] Serotonin promotes pulmonary arterial smooth muscle cell and fi broblast proliferation, pulmonary arterial vasoconstriction, and local microthrombosis-all key pathogenic features in PAH. These effects of serotonin are mediated by interactions between serotonin and its transporter and receptors. [6][7][8][9][10] In particular, the serotonin transporter (SERT) plays a key role in the pathogenesis of experimental PH; in animal models, SERT overexpression predisposes to the development of PH, whereas pharmacologic blockade of SERT is protective. 1,[11][12][13][14] In humans, a functional polymorphism in the SERT gene correlates with more severe PH associated with COPD. 15 Selective serotonin reuptake inhibitors (SSRIs) act via blockade of SERT, resulting in an extracellular accumulation of serotonin and increased activation of serotonin receptors. 16 SSRIs have been associated with both protection against and regression of PH in animal models, suggesting a possible role in the treatment of PAH in humans. 1,14,17 Early observational studies have suggested therapeutic effi cacy of SSRIs in patients with Background: Selective serotonin reuptake inhibitors (SSRIs) have been suggested to offer therapeutic benefi t in patients with pulmonary arterial hypertension (PAH). We conducted two analyses to explore the association between SSRI use and PAH outcomes using the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry). Methods: First, new users (SSRI-naive patients who initiated treatment after enrollment, incident use analysis, n 5 220) were matched (1:2) with non-SSRI users (nonusers, n 5 440) by enrollment center, sex, date of most recent visit, age, and 6-min walk distance. Second, a cross-sectional design was used to compare nonusers (n 5 2,463), high-affi nity SSRI users (n 5 430), and non-high-affi nity SSRI users (n 5 125) at enrollment. Mortality and a composite end point defi ned by events indicative of clinical worsening were evaluated. Results: New users had a higher risk of death (unadjusted hazard ratio [HR], 1.74; 95% CI, 1.19-2.54; P 5 .004) and were less likely to be free from the composite end point 2 years after enrollment vs nonusers (25.7% vs 43.2%, respectively; P , .001). Similarly, among prevalent SSRI users (patients with a history of SSRI use at enrollment), high-affi nity SSRI users were less likely to be free from the composite end point vs nonusers (unadjusted HR, 1.20; 95% CI, 1.07-1.36; P 5 .003). In both analyses, differences in outcome were maintained after adjustment for clinical variables previously associated with PAH outcomes. Conclusions:In a large population of patients with PAH, incident SSRI use was associated with increased mortality and a greater risk of clinical worsening, although we could ...

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Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

Cited by 85 publications

References 72 publications

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

New hypothesis and treatment targets of depression: an integrated view of key findings

Use of Selective Serotonin Reuptake Inhibitors and Outcomes in Pulmonary Arterial Hypertension

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