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脑源性神经营养因子(BDNF)和神经生长因子(NGF)作为抑郁症关键调节因子的直接和间接证据:抗抑郁药治疗的作用

Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment.

作者信息

Mondal Amal Chandra, Fatima Mahino

机构信息

a Laboratory of Cellular and Molecular Neurobiology , School of Life Sciences, Jawaharlal Nehru University , New Delhi , India.

出版信息

Int J Neurosci. 2019 Mar;129(3):283-296. doi: 10.1080/00207454.2018.1527328. Epub 2018 Nov 27.

Abstract

PURPOSE

Depression is one of the most prevalent, recurrent and life-threatening mental illnesses. However, the precise mechanism underlying the disorder is not yet clearly understood. It is therefore, essential to identify the novel biomarkers which may help in the development of effective treatment.

METHODS

In this milieu, the profile of the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were considered as biomarkers in the light of pathophysiology of depression and its treatment.

RESULTS

Previously, we have reported that BDNF level in the postmortem brain of suicide victims was significantly lower than those of normal controls. We also found decreased BDNF levels in the specific brain regions of the learned helplessness model of depression in rat, and was found to increase normal level following chronic fluoxetine hydrochloride treatment. NGF is another important member of neurotrophin, which is dysregulated in the pathophysiology of depression in some models of peripheral nerve damage and stress. The results shown evidences of the effect of antidepressants on modulating depression via the NGF in preclinical and clinical models of depression, but conflicted, therefore make it currently difficult to affirm the therapeutic role of antidepressants.

CONCLUSIONS

Here, we review some of the preclinical and clinical studies aimed at disclosing the role of BDNF and NGF mediated pathophysiological mechanisms of depression and the new therapeutic approaches targeting those key molecules. In addition, an important link between BDNF, NGF and depression has been discussed in the light of current existing knowledge.

摘要

目的

抑郁症是最常见、易复发且危及生命的精神疾病之一。然而,该疾病背后的确切机制尚未完全明确。因此,识别可能有助于开发有效治疗方法的新型生物标志物至关重要。

方法

在此背景下,鉴于抑郁症的病理生理学及其治疗方法,脑源性神经营养因子(BDNF)和神经生长因子(NGF)的概况被视为生物标志物。

结果

此前,我们报道自杀受害者死后大脑中的BDNF水平显著低于正常对照组。我们还发现,在大鼠抑郁症习得性无助模型的特定脑区中BDNF水平降低,并且在慢性盐酸氟西汀治疗后发现其水平恢复正常。NGF是神经营养因子的另一个重要成员,在一些外周神经损伤和应激模型中,其在抑郁症的病理生理学中失调。结果显示了在抑郁症的临床前和临床模型中,抗抑郁药通过NGF调节抑郁症的证据,但存在矛盾之处,因此目前难以肯定抗抑郁药的治疗作用。

结论

在此,我们综述了一些旨在揭示BDNF和NGF介导的抑郁症病理生理机制的作用以及针对这些关键分子的新治疗方法的临床前和临床研究。此外,根据现有知识讨论了BDNF、NGF与抑郁症之间的重要联系。

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