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长期锂治疗以亚治疗浓度增加皮质和海马神经元中的细胞内和细胞外脑源性神经营养因子 (BDNF)。

Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at subtherapeutic concentrations.

机构信息

Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil.

出版信息

Bipolar Disord. 2016 Dec;18(8):692-695. doi: 10.1111/bdi.12449. Epub 2016 Nov 24.

Abstract

OBJECTIVES

The putative neuroprotective effects of lithium treatment rely on the fact that it modulates several homeostatic mechanisms involved in the neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. The aim of this study was to evaluate the effects of subtherapeutic and therapeutic concentrations of chronic lithium treatment on brain-derived neurotrophic factor (BDNF) synthesis and secretion.

METHODS

Primary cultures of cortical and hippocampal neurons were treated with different subtherapeutic (0.02 and 0.2 mM) and therapeutic (2 mM) concentrations of chronic lithium treatment in cortical and hippocampal cell culture.

RESULTS

Lithium treatment increased the intracellular protein expression of cortical neurons (10% at 0.02 mM) and hippocampal neurons (28% and 14% at 0.02 mM and 0.2 mM, respectively). Extracellular BDNF of cortical neurons increased 30% and 428% at 0.02 and 0.2 mM, respectively and in hippocampal neurons increased 44% at 0.02 mM.

CONCLUSION

The present study indicates that chronic, low-dose lithium treatment up-regulates BDNF production in primary neuronal cell culture.

摘要

目的

锂治疗的潜在神经保护作用依赖于这样一个事实,即它调节了神经营养反应、自噬、氧化应激、炎症和线粒体功能中涉及的几种动态平衡机制。锂是治疗双相情感障碍和重度抑郁症的急性和长期管理的成熟治疗选择。本研究的目的是评估亚治疗和治疗浓度的慢性锂治疗对脑源性神经营养因子 (BDNF) 合成和分泌的影响。

方法

原代皮质和海马神经元培养物分别用不同的亚治疗(0.02 和 0.2 mM)和治疗(2 mM)浓度的慢性锂处理进行皮质和海马细胞培养。

结果

锂处理增加了皮质神经元(0.02 mM 时增加 10%)和海马神经元(0.02 mM 和 0.2 mM 时分别增加 28%和 14%)的细胞内蛋白表达。皮质神经元的细胞外 BDNF 分别增加了 30%和 428%,而 0.02 mM 时海马神经元的细胞外 BDNF 增加了 44%。

结论

本研究表明,慢性低剂量锂治疗可上调原代神经元细胞培养物中 BDNF 的产生。

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