The Effect of Recombinant Erythropoietin on Plasma Brain Derived Neurotrophic Factor Levels in Patients with Affective Disorders: A Randomised Controlled Study

Vinberg, Maj; Miskowiak, Kamilla Woznica; Hoejman, Pernille; Pedersen, Maria; Kessing, Lars Vedel

doi:10.1371/journal.pone.0127629

Cited by 19 publications

(10 citation statements)

References 63 publications

(83 reference statements)

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“…Recently, clinical evidence of the procognitive potential of EPO has been proved by a randomized controlled trial (RCT) involving moderately depressed patients with treatment-resistant depression ( N = 40) [ 168 ]. EPO also down-regulated plasma BDNF levels in patients with treatment-resistant depression (TRD; N = 40) [ 169 ]. Taken together, these seven clinical findings ( Table 1 ) suggested that EPO may provide a therapeutic option for patients with depression.…”

Section: Epo In the Treatment Of Depressionmentioning

confidence: 99%

Erythropoietin Pathway: A Potential Target for the Treatment of Depression

Cheng

Wang

et al. 2016

IJMS

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During the past decade, accumulating evidence from both clinical and experimental studies has indicated that erythropoietin may have antidepressant effects. In addition to the kidney and liver, many organs have been identified as secretory tissues for erythropoietin, including the brain. Its receptor is expressed in cerebral and spinal cord neurons, the hypothalamus, hippocampus, neocortex, dorsal root ganglia, nerve axons, and Schwann cells. These findings may highlight new functions for erythropoietin, which was originally considered to play a crucial role in the progress of erythroid differentiation. Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling pathways including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system. This is particularly true for the hippocampus, which is possibly related to learning, memory, neurocognitive deficits and mood alterations. Thus, the influence of erythropoietin on the downstream pathways known to be involved in the treatment of depression makes the erythropoietin-related pathway an attractive target for the development of new therapeutic approaches. Focusing on erythropoietin may help us understand the pathogenic mechanisms of depression and the molecular basis of its treatment.

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Section: Epo In the Treatment Of Depressionmentioning

confidence: 99%

Erythropoietin Pathway: A Potential Target for the Treatment of Depression

Cheng

Wang

et al. 2016

IJMS

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“…More and more experimental compounds are also being confirmed as capable of regulating depressive progresses via activating the BDNF signaling pathway ( Osborn et al, 2013 ; Yang et al, 2015 ). More importantly, the hippocampal BDNF and other neurotrophic factors have been shown to be reduced in patients with bipolar disorder and major depression ( Polyakova et al, 2015 ; Vinberg et al, 2015 ). Therefore, increasing BDNF protein expression might be a common pathway for antidepressants to exert their therapeutic actions, and searching agents that can increase BDNF protein expression is beneficial for the development of new antidepressants.…”

Section: Discussionmentioning

confidence: 99%

Z-Guggulsterone Produces Antidepressant-Like Effects in Mice through Activation of the BDNF Signaling Pathway

Liu

Wang

et al. 2017

International Journal of Neuropsychopharmacology

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Background:Z-guggulsterone, an active compound extracted from the gum resin of the tree Commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress mouse model of depression.Methods:The effects of Z-guggulsterone were assessed in mice with the tail suspension test and forced swimming test. Z-guggulsterone was also investigated in the chronic unpredictable stress model of depression with fluoxetine as the positive control. Changes in hippocampal neurogenesis as well as the brain-derived neurotrophic factor signaling pathway after chronic unpredictable stress/Z-guggulsterone treatment were investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressant-like mechanisms of Z-guggulsterone.Results:Z-guggulsterone (10, 30 mg/kg) administration protected the mice against the chronic unpredictable stress-induced increases in the immobile time in the tail suspension test and forced swimming test and also reversed the reduction in sucrose intake in sucrose preference experiment. Z-guggulsterone (10, 30 mg/kg) administration prevented the reductions in brain-derived neurotrophic factor protein expression levels as well as the phosphorylation levels of cAMP response element binding protein, extracellular signal-regulated kinase 1/2, and protein kinase B in the hippocampus and cortex induced by chronic unpredictable stress. Z-guggulsterone (10, 30 mg/kg) treatment also improved hippocampal neurogenesis in chronic unpredictable stress-treated mice. Blockade of the brain-derived neurotrophic factor signal, but not the monoaminergic system, attenuated the antidepressant-like effects of Z-guggulsterone.Conclusions:Z-guggulsterone exhibits antidepressant activity via activation of the brain-derived neurotrophic factor signaling pathway and upregulation of hippocampal neurogenesis.

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“…Recombinant erythropoietin was characterized as a tissue protective factor (Elliot and Sinclair 2012, Rocha et al 2015, Vinberg et al 2015. Protective effect of erythropoietin is dose-dependent and receptor-dependent.…”

Section: Recombinant Erythropoietin (Epoetin)mentioning

confidence: 99%

Pleiotropic effects of Erythropoietin. Influence of Erythropoietin on processes of mesenchymal stem cells differentiation

Zubareva¹,

Nadezhdin²,

Burda³

et al. 2019

RRP

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Structure and synthesis of Erythropoietin: Erythropoietin (EPO) is a glycoprotein hormone.Recombinant Erythropoietin (Epoetin): Human recombinant erythropoietin is characterised as a factor which stimulates differentiation and proliferation of erythroid precursor cells, and as a tissue protective factor.Anti-ischemic effects of recombinant Erythropoietin: Erythropoietin is one of the most perspective humoral agents which are involved in the preconditioning phenomenon.Erythropoietin receptors and signal transduction pathways: Erythropoietin effects on cells through their interconnection with erythropoietin receptors, which triggers complex intracellular signal cascades, such as JAK2/STAT signaling pathway, phosphatidylinositol 3-kinase (PI3K), protein kinase C, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB signaling pathways.Mechanisms of the effect of Erythropoietin on hematopoietic and non-hematopoietic cells and tissues: In addition to regulation of haemopoiesis, erythropoietin mediates bone formation as it has an effect on hematopoietic stem cells and osteoblastic niche, and this illustrates connection between the processes of haematopoiesis and osteopoiesis which take place in the red bone marrow.The effect of Erythropoietin on mesenchymal stem cells and process of bone tissue formation: Erythropoietin promotes mesenchymal stem cells proliferation, migration and differentiation in osteogenic direction. The evidence of which is expression of bone phenotype by cells under the influence of EPO, including activation of bone specific transcription factors Runx2, osteocalcin and bone sialoprotein.Conclusion: Erythropoietin has a pleiotropic effect on various types of cells and tissues. But the mechanisms which are involved in the process of bone tissue restoration via erythropoietin are still poorly understood.

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The Effect of Recombinant Erythropoietin on Plasma Brain Derived Neurotrophic Factor Levels in Patients with Affective Disorders: A Randomised Controlled Study

Cited by 19 publications

References 63 publications

Erythropoietin Pathway: A Potential Target for the Treatment of Depression

Erythropoietin Pathway: A Potential Target for the Treatment of Depression

Z-Guggulsterone Produces Antidepressant-Like Effects in Mice through Activation of the BDNF Signaling Pathway

Pleiotropic effects of Erythropoietin. Influence of Erythropoietin on processes of mesenchymal stem cells differentiation

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