Mood Stabilizers (Lamotrigine, Lithium, and Valproic Acid) Decrease Bipolar Disease Model (Ouabain)-Induced Oxidative Stress and Apoptosis Through the Inhibition of the TRPM2 Channel in Neuronal Cells.

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Esra Nur Kaplan, İbrahim Eren, Mustafa Nazıroğlu
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引用次数: 0

Abstract

Background: Bipolar disease (BD) has been strongly associated with the etiologies of mitochondrial reactive oxygen species (mROS), apoptosis, and Ca2+ influx. With the exception of BD, a number of neurological disorders have been linked to apoptosis and neuronal death mediated by mROS-dependent activated TRPM2 channel stimulation. Lamotrigine (LMT), lithium (Li), and valproic acid (VPA) are mood stabilizers in BD, and they have strong antioxidant roles. However, the molecular mechanisms underlying LMT, Li, and VPA neuroprotection through TRPM2 channel inhibiton remain elusive in BD.

Aim: We evaluated the protective actions of LMT, Li, and VPA on BD (ouabain, OUA)-induced oxidative neurotoxicity in SH-SY5Y neuronal cells by modulating TRPM2.

Methods: The SH-SY5Y cells were divided into nine groups as follows: control, Li, VPA, LMT, OUA, OUA + Li, OUA + VPA, LMT + VPA, and OUA + TRPM2 antagonists (N-(p-amylcinnamoyl)anthranilic acid or carvacrol).

Results: OUA exposure and TRPM2 agonist (H2O2 and ADP-ribose)-induced TRPM2 stimulation and TRPM2 current densities were downregulated by the treatments of TRPM2 antagonist, Li, VPA, and LMT. The OUA-induced upregulations of mROS, cytosolic ROS, lipid peroxidation, mitochondrial membrane dysfunction, apoptosis, Zn2+, cell death, and caspase-3, -8, and -9 values were also downregulated through the increases of cell viability, glutathione, and glutathione peroxidase by the treatments.

Conclusions: The treatments of Li, VPA, and LMT modulate OUA-mediated mROS, apoptosis, Zn2+, glutathione, and TRPM2-mediated excess Ca2+ influx. This could potentially offer protection against BD linked to elevated levels of mROS, Ca2+, and Zn2+.

情绪稳定剂(拉莫三嗪、锂和丙戊酸)通过抑制神经元细胞中的TRPM2通道减少双相情感障碍模型(瓦巴因)诱导的氧化应激和细胞凋亡。
背景:双相情感障碍(BD)与线粒体活性氧(mROS)、细胞凋亡和Ca2+内流的病因密切相关。除BD外,许多神经系统疾病都与mros依赖性激活TRPM2通道刺激介导的细胞凋亡和神经元死亡有关。拉莫三嗪(LMT)、锂(Li)和丙戊酸(VPA)是BD患者的情绪稳定剂,具有较强的抗氧化作用。然而,LMT、Li和VPA通过抑制TRPM2通道保护BD神经的分子机制尚不清楚。目的:研究LMT、Li和VPA通过调节TRPM2对BD(瓦阿因、OUA)诱导的SH-SY5Y神经元细胞氧化神经毒性的保护作用。方法:将SH-SY5Y细胞分为对照组、Li组、VPA组、LMT组、OUA组、OUA + Li组、OUA + VPA组、LMT + VPA组、OUA + TRPM2拮抗剂(N-(对戊肉桂基)邻氨基苯甲酸或香芹酚)组。结果:OUA暴露和TRPM2激动剂(H2O2和adp核糖)诱导的TRPM2刺激和TRPM2电流密度被TRPM2拮抗剂、Li、VPA和LMT处理下调。oua诱导的mROS、胞质ROS、脂质过氧化、线粒体膜功能障碍、凋亡、Zn2+、细胞死亡和caspase-3、-8和-9值的上调也通过处理增加细胞活力、谷胱甘肽和谷胱甘肽过氧化物酶而下调。结论:Li、VPA和LMT可调节oua介导的mrs、凋亡、Zn2+、谷胱甘肽和trpm2介导的过量Ca2+内流。这可能潜在地提供与升高的mROS、Ca2+和Zn2+水平相关的BD保护。
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来源期刊
Bipolar Disorders
Bipolar Disorders 医学-精神病学
CiteScore
8.20
自引率
7.40%
发文量
90
审稿时长
6-12 weeks
期刊介绍: Bipolar Disorders is an international journal that publishes all research of relevance for the basic mechanisms, clinical aspects, or treatment of bipolar disorders and related illnesses. It intends to provide a single international outlet for new research in this area and covers research in the following areas: biochemistry physiology neuropsychopharmacology neuroanatomy neuropathology genetics brain imaging epidemiology phenomenology clinical aspects and therapeutics of bipolar disorders Bipolar Disorders also contains papers that form the development of new therapeutic strategies for these disorders as well as papers on the topics of schizoaffective disorders, and depressive disorders as these can be cyclic disorders with areas of overlap with bipolar disorders. The journal will consider for publication submissions within the domain of: Perspectives, Research Articles, Correspondence, Clinical Corner, and Reflections. Within these there are a number of types of articles: invited editorials, debates, review articles, original articles, commentaries, letters to the editors, clinical conundrums, clinical curiosities, clinical care, and musings.
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