Low Brain-Derived Neurotrophic Factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity

Karege, Félicien; Bondolfi, Guido; Gervasoni, Nicola; Schwald, Michèle; Aubry, Jean‐Michel; Bertschy, Gilles

doi:10.1016/j.biopsych.2005.01.008

Cited by 517 publications

(374 citation statements)

References 54 publications

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“…[50][51][52] Furthermore, serum BDNF in living depressed patients is abnormally low, but can be restored following pharmacological antidepressant treatment. [53][54][55][56][57][58] The BDNF hypothesis of depression: the argument against…”

Section: Clinical Evidencementioning

confidence: 99%

“…Human BDNF and TrkB expression are decreased in depressed patients Post-mortem hippocampal mRNA and protein 49 Serum protein from living patients [51][52][53]56 BDNF levels are increased in patients receiving pharmacological antidepressants Post-mortem hippocampal protein 48 Serum protein from living patients [53][54][55][56] BDNF levels refer to mRNA apart from where specified. Abbreviations: AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BDNF, brain-derived neurotrophic factor; ECS, electroconvulsive shock; MAOi, monoamine oxidase inhibitor; NARI, noradrenalin reuptake inhibitor; NMDA, N-methyl-D-aspartic acid; SNRI, serotonin and noradrenalin reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TMS, transcranial magnetic stimulation; TrkB, tyrosine kinase receptor B; VTA, ventral tegmental area.…”

Section: Midbrain 27mentioning

confidence: 99%

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Is it time to reassess the BDNF hypothesis of depression?

2007

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The brain-derived neurotrophic factor (BDNF) hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and that its restoration may underlie the therapeutic efficacy of antidepressant treatment. While this theory has received considerable experimental support, an increasing number of studies have generated evidence which is not only inconsistent, but also directly contradicts the hypothesis. This article provides a critical review of the clinical and preclinical studies which have been responsible for this controversy, outlining pharmacological, behavioural and genetic evidence which demonstrates the contrasting role of BDNF in regulating mood and antidepressant effects throughout the brain. I will also review key studies, both human and animal, which have investigated the association of a BDNF single-nucleotide polymorphism (Val66Met) with depression pathogenesis, and detail the number of inconsistencies which also afflict this novel area of BDNF research. The article will conclude by discussing why now is a critical time to reassess the original BDNF hypothesis of depression, and look towards the formation of new models that can provide a more valid account of the complex relationships between growth factors, mood disorders and their treatment.

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Section: Clinical Evidencementioning

confidence: 99%

Section: Midbrain 27mentioning

confidence: 99%

Is it time to reassess the BDNF hypothesis of depression?

2007

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“…Furthermore, there is strong evidence that peripheral growth factors, including BDNF, pro-inflammatory cytokines, endocrine factors, and metabolic markers contribute to the pathophysiology of major depressive disorder and antidepressant response (Schmidt et al, 2011). As a matter of fact BDNF levels are decreased in the blood of depressed patients and can be normalized with successful antidepressant treatment (Sen et al, 2008), although the origin and role of serum BDNF is unclear (Karege et al, 2005). Chronic peripheral administration of BDNF produces antidepressant and anxiolytic behavioral responses in animal models, increases the survival rate of newborn neurons, and increases BDNFmediated signaling in the adult hippocampus (Schmidt and Duman, 2010), an evidence that peripheral BDNF has functional actions within the brain and on behavior, and that serum BDNF may be a relevant biomarker for depression and treatment response.…”

Section: Introductionmentioning

confidence: 99%

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Bahí

Chandrasekar

Dreyer

2014

Psychoneuroendocrinology

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Summary Several lines of evidences suggest that the brain-derived neutrophic factor (BDNF) is implicated in the pathophysiology of depression. However, the molecular mechanisms are not fully understood. In the current study we aimed to investigate how genetic modulation of BDNF in the hippocampus using microRNa124a (miR124a)-expressing lentiviral vectors (LV) might affect depression-like behavior in adult rats. For this purpose, we assessed the expression level of miR124a and its direct target BDNF in the hippocampus and the cortex after 21-days exposure to social defeat stress. Results demonstrated that miR124a was up-regulated in the hippocampus but not in the cortex. In contrast, and as expected, BDNF transcripts were down-regulated. In a different set of experiments, male Wistar rats received bilateral intra-hippocampal or intracortical infusions of BDNF-and miR124a-expressing lentiviral vectors and depression-like behavior was assessed after 21-days social defeat stress using the novelty suppressed feeding, the sucrose preference and the forced swim tests. The results indicated that miR124a overexpression exacerbated depression-like behavior. However, an anti-depressant like effect was observed when BDNF or miR124a-silencers (siR124a) were injected into the hippocampus. Importantly, when expressed into the cortex, LV-miR124a, LV-siR124a and LV-BDNF had no effect on depression. Our findings indicate that hippocampal miR124a and its direct target BDNF play an important role in depression-like behavior. Taken together, the current results reveal, for the first time, a potential molecular regulation of miR124a on BDNF, and the pronounced behavioral consequences of this regulation shed light on the mechanisms underlying BDNF anti-depressant potential. #

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“…Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of neurotrophic factors, and its primary receptor TrkB seem to be particularly relevant factors involved in both the development of mood disorders and the action of antidepressants (Altar, 1999;Nestler et al, 2002;Castrén, 2005;Castrén et al, 2007). BDNF levels are reduced in mood disorders and preclinical depression models, and long-term antidepressant treatment enhances brain BDNF gene expression and signaling (Nibuya et al, 1995(Nibuya et al, , 1996Smith et al, 1995;Russo-Neustadt et al, 1999;Chen et al, 2001b;Karege et al, 2002Karege et al, , 2005. A growing body of evidence suggests that BDNF-mediated TrkB signaling is both sufficient and necessary for antidepressant-like behaviors in rodents.…”

Section: Introductionmentioning

confidence: 99%

Pharmacologically Diverse Antidepressants Rapidly Activate Brain-Derived Neurotrophic Factor Receptor TrkB and Induce Phospholipase-Cγ Signaling Pathways in Mouse Brain

Rantamäki

Hendolin²,

Kankaanpää

et al. 2007

Neuropsychopharmacol

275

205

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Previous studies suggest that brain-derived neurotrophic factor and its receptor TrkB are critically involved in the therapeutic actions of antidepressant drugs. We have previously shown that the antidepressants imipramine and fluoxetine produce a rapid autophosphorylation of TrkB in the rodent brain. In the present study, we have further examined the biochemical and functional characteristics of antidepressant-induced TrkB activation in vivo. We show that all the antidepressants examined, including inhibitors of monoamine transporters and metabolism, activate TrkB rapidly in the rodent anterior cingulate cortex and hippocampus. Furthermore, the results indicate that acute and long-term antidepressant treatments induce TrkB-mediated activation of phospholipase-Cg1 (PLCg1) and increase the phosphorylation of cAMP-related element binding protein, a major transcription factor mediating neuronal plasticity. In contrast, we have not observed any modulation of the phosphorylation of TrkB Shc binding site, phosphorylation of mitogen-activated protein kinase or AKT by antidepressants. We also show that in the forced swim test, the behavioral effects of specific serotonergic antidepressant citalopram, but not those of the specific noradrenergic antidepressant reboxetine, are crucially dependent on TrkB signaling. Finally, brain monoamines seem to be critical mediators of antidepressant-induced TrkB activation, as antidepressants reboxetine and citalopram do not produce TrkB activation in the brains of serotonin-or norepinephrine-depleted mice. In conclusion, our data suggest that rapid activation of the TrkB neurotrophin receptor and PLCg1 signaling is a common mechanism for all antidepressant drugs.

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Low Brain-Derived Neurotrophic Factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity

Cited by 517 publications

References 54 publications

Is it time to reassess the BDNF hypothesis of depression?

Is it time to reassess the BDNF hypothesis of depression?

Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats

Pharmacologically Diverse Antidepressants Rapidly Activate Brain-Derived Neurotrophic Factor Receptor TrkB and Induce Phospholipase-Cγ Signaling Pathways in Mouse Brain

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