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利鲁唑刺激人血小板释放脑源性神经营养因子。

Riluzole stimulates BDNF release from human platelets.

作者信息

Türck Patrick, Frizzo Marcos Emílio

机构信息

Department of Morphological Sciences, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500, 90050-170 Porto Alegre, RS, Brazil.

出版信息

Biomed Res Int. 2015;2015:189307. doi: 10.1155/2015/189307. Epub 2015 Jan 6.

Abstract

Brain-derived neurotrophic factor (BDNF) has several functions in the central nervous system, where it contributes to brain development and its functionality through affecting neuronal survival and activity and also modulating neurotransmitter levels. This neurotrophin is also found in the serum, but its origin and peripheral function remain unknown. Although the source of circulating BDNF is uncertain, it is stored in platelets and can be released through pharmacological treatment. Decreased levels of BDNF in the serum have been related to the pathophysiology of depression, and this relationship is reinforced by the reversal of this condition by treatment with antidepressants. Recently, riluzole has been proposed for the treatment of depression because it has the ability to lower extracellular glutamate levels and increase BDNF expression; and both mechanisms could be associated with its antidepressant action. Considering that riluzole enhances BDNF levels in the serum of patients, we investigated if treatment with this drug could stimulate the release of this neurotrophin from human platelets obtained from healthy subjects. When platelets were incubated with riluzole for 4 h, the basal value of BDNF (92.9 ± 11.1 pg 10(-6) platelets) was significantly increased (P < 0.05, n = 27). This stimulatory effect was achieved at low concentrations of riluzole (from 10 µM) and was not observed when platelets were incubated with the drug for 24 h. The direct action of riluzole evoking BDNF release from human platelets at therapeutic concentrations is important and may contribute to the understanding of its mechanisms of action in the treatment of depression.

摘要

脑源性神经营养因子(BDNF)在中枢神经系统中具有多种功能,它通过影响神经元的存活和活性以及调节神经递质水平,对大脑发育及其功能发挥作用。这种神经营养因子在血清中也有发现,但其来源和外周功能尚不清楚。尽管循环BDNF的来源不确定,但它储存在血小板中,并且可以通过药物治疗释放出来。血清中BDNF水平降低与抑郁症的病理生理学有关,而抗抑郁药治疗可逆转这种情况,从而强化了这种关系。最近,利鲁唑被提议用于治疗抑郁症,因为它有能力降低细胞外谷氨酸水平并增加BDNF表达;这两种机制都可能与其抗抑郁作用有关。鉴于利鲁唑可提高患者血清中的BDNF水平,我们研究了用这种药物治疗是否能刺激从健康受试者获得的人血小板释放这种神经营养因子。当血小板与利鲁唑孵育4小时时,BDNF的基础值(92.9±11.1 pg 10^(-6)血小板)显著增加(P<0.05,n = 27)。这种刺激作用在低浓度利鲁唑(从10µM起)时即可实现,而当血小板与药物孵育24小时时未观察到这种作用。利鲁唑在治疗浓度下直接促使人类血小板释放BDNF的作用很重要,可能有助于理解其在抑郁症治疗中的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97b1/4300019/c6bde7276f26/BMRI2015-189307.002.jpg

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