Upregulation of blood proBDNF and its receptors in major depression

Zhou, Li; Xiong, Jing; Lim, Yoon Pin; Ruan, Ye Chun; Huang, Chaohong; Zhu, Yuanyuan; Zhong, Jin‐Hua; Xiao, Zhi‐Cheng; Zhou, Xin‐Fu

doi:10.1016/j.jad.2013.03.002

Cited by 131 publications

(111 citation statements)

References 35 publications

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“…Furthermore, we have previously found that the level of proBDNF in the serum and lymphocytes is increased in the patients with MDD (Zhou et al, 2013), suggesting that proBDNF is also dysregulated in MDD. The above findings may suggest that the upregulation of proBDNF is associated with the development and progression of mood disorders.…”

Section: Discussionmentioning

confidence: 93%

“…Clinical studies have shown that serum levels of proBDNF are increased in patients with MDD (Zhou et al, 2013); however, whether chronic stress can regulate proBDNF levels in the brain is still unknown. In this study, we have used an UCMS model of mice to examine the expression profile of proBDNF in the brain.…”

Section: Chronic Stress Increased Probdnf Levels In Mouse Brainsmentioning

confidence: 99%

“…It is well established that BDNF regulates neuronal survival via activation of a membrane receptor, TrkB, whereas proBDNF regulates neuronal death via activating membrane receptor p75 NTR -mediated apoptotic signaling that requires another membrane receptor called sortilin (Lee et al, 2001;Nykjaer et al, 2004;Teng et al, 2005). Our previous clinical study has shown that the blood proBDNF levels as well as its co-receptors, p75 NTR and sortilin, are increased in the patients with MDD (Zhou et al, 2013). However, the role of proBDNF and its signaling in the central nervous system in mood regulation remains unknown.…”

Section: Introductionmentioning

confidence: 98%

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ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

Bai

Ruan

Yang

et al. 2016

Neuropsychopharmacol

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104

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Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75 NTR /sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific antiproBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

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Section: Discussionmentioning

confidence: 93%

Section: Chronic Stress Increased Probdnf Levels In Mouse Brainsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

Bai

Ruan

Yang

et al. 2016

Neuropsychopharmacol

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104

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“…The tissue samples were homogenized, and levels of mature BDNF in the homogenate were determined by a highly specific, mature BDNF ELISA kit, as previously described (20). The procedure is highly specific for mature BDNF only and does not detect proBDNF or the other neurotrophins, such as neurotrophins-3 and -4 and nerve growth factor.…”

Section: Reverse Transcription-quantitative Polymerase Chain Reactionmentioning

confidence: 99%

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

et al. 2015

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Abstract. There are two forms of brain-derived neurotrophic factor (BDNF), precursor of BDNF (proBDNF) and mature BDNF, which each exert opposing effects through two different transmembrane receptor signaling systems, consisting of p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB). Previous studies have demonstrated that proBDNF promotes cell death and inhibits the growth and migration of C6 glioma cells through p75NTR in vitro, while mature BDNF has opposite effects on C6 glioma cells. It is hypothesized that mature BDNF is essential in the development of malignancy in gliomas. However, histological data obtained in previous studies were unable distinguish mature BDNF from proBDNF due to the lack of specific antibodies. The present study investigated the expression of mature BDNF using a specific sheep monoclonal anti-mature BDNF antibody in 42 human glioma tissues of different grades and 10 control tissues. The correlation between mature BDNF and TrkB was analyzed. Mature BDNF expression was significantly increased in high-grade gliomas, and was positively correlated with the malignancy of the tumor and TrkB receptor expression. The present data have demonstrated that increased levels of mature BDNF contribute markedly to the development of malignancy of human gliomas through the primary BDNF receptor TrkB.

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“…70 proBDNF has been less widely studied than the mature form of BDNF, but the two appear to differ functionally (in terms of their effects on tyrosine receptor kinase B receptors) and recent evidence suggests that while mature BDNF may be reduced in depression, proBDNF may be overproduced. 72 Nerve growth factor assessed peripherally has also been reported as lower in depression than in controls in a meta-analysis, but may not be altered by antidepressant treatment despite being most attenuated in patients with more severe depression. 73 Similar findings have been reported in a meta-analysis for glial cell line-derived neurotrophic factor.…”

Section: Growth Factor Findings In Depressionmentioning

confidence: 97%

Biomarkers for Depression: Recent Insights, Current Challenges and Future Prospects

Strawbridge¹,

Young

Cleare³

2018

FOC

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A plethora of research has implicated hundreds of putative biomarkers for depression, but has not yet fully elucidated their roles in depressive illness or established what is abnormal in which patients and how biologic information can be used to enhance diagnosis, treatment and prognosis. This lack of progress is partially due to the nature and heterogeneity of depression, in conjunction with methodological heterogeneity within the research literature and the large array of biomarkers with potential, the expression of which often varies according to many factors. We review the available literature, which indicates that markers involved in inflammatory, neurotrophic and metabolic processes, as well as neurotransmitter and neuroendocrine system components, represent highly promising candidates. These may be measured through genetic and epigenetic, transcriptomic and proteomic, metabolomic and neuroimaging assessments. The use of novel approaches and systematic research programs is now required to determine whether, and which, biomarkers can be used to predict response to treatment, stratify patients to specific treatments and develop targets for new interventions. We conclude that there is much promise for reducing the burden of depression through further developing and expanding these research avenues.

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Upregulation of blood proBDNF and its receptors in major depression

Cited by 131 publications

References 35 publications

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress

Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues

Biomarkers for Depression: Recent Insights, Current Challenges and Future Prospects

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