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伏隔核深部脑刺激治疗强迫症的潜在机制

Potential therapeutic mechanism of deep brain stimulation of the nucleus accumbens in obsessive-compulsive disorder.

作者信息

Shi Yifeng, Wang Mengqi, Xiao Linglong, Gui Luolan, Zheng Wen, Bai Lin, Su Bo, Li Bin, Xu Yangyang, Pan Wei, Zhang Jie, Wang Wei

机构信息

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Laboratory of Clinical Proteomics and Metabolomics, Frontiers Science Center for Disease-Related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Institutes for Systems Genetics, Sichuan University, Chengdu, Sichuan, China.

出版信息

Front Cell Neurosci. 2023 Jan 4;16:1057887. doi: 10.3389/fncel.2022.1057887. eCollection 2022.

Abstract

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) (NAc-DBS) is an effective solution to refractory obsessive-compulsive disorder (OCD). However, evidence for the neurobiological mechanisms of OCD and the effect of NAc-DBS is still lacking. One hypothesis is that the electrophysiological activities in the NAc are modulated by DBS, and another hypothesis is that the activities of neurotransmitters in the NAc are influenced by DBS. To investigate these potential alterations, rats with quinpirole (QNP)- induced OCD were treated with DBS of the core part of NAc. Then, extracellular spikes (SPK) and local field potentials (LFP) in the NAc were recorded, and the levels of relevant neurotransmitters and related proteins were measured. Analysis of SPK revealed that the firing rate was decreased and the firing pattern was changed after NAc-DBS, and analysis of LFP showed that overall power spectral density (PSD) levels were reduced after NAc-DBS. Additionally, we found that the relative powers of the theta band, alpha band and beta band were increased in OCD status, while the relative powers of the delta band and gamma band were decreased. This pathological pattern of power distribution was reformed by NAc-DBS. Furthermore, we found that the local levels of monoamines [dopamine (DA) and serotonin (5-HT)] and amino acids [glutamate (Glu) and gamma-aminobutyric acid (GABA)] in the NAc were increased in OCD status, and that the expression of the two types of DA receptors in the NAc exhibited an opposite change. These abnormalities could be reversed by NAc-DBS. These findings provide a more comprehensive understanding about the function of the NAc in the pathophysiology of OCD and provide more detailed evidence for the potential effect of NAc-DBS.

摘要

伏隔核深部脑刺激(NAc-DBS)是治疗难治性强迫症(OCD)的有效方法。然而,关于OCD的神经生物学机制以及NAc-DBS的作用的证据仍然不足。一种假说是,NAc中的电生理活动受DBS调节,另一种假说是,NAc中神经递质的活动受DBS影响。为了研究这些潜在的变化,对喹吡罗(QNP)诱导的OCD大鼠进行了NAc核心部分的DBS治疗。然后,记录NAc中的细胞外尖峰(SPK)和局部场电位(LFP),并测量相关神经递质和相关蛋白的水平。SPK分析显示,NAc-DBS后放电率降低且放电模式改变,LFP分析表明,NAc-DBS后总体功率谱密度(PSD)水平降低。此外,我们发现,在OCD状态下,θ波段、α波段和β波段的相对功率增加,而δ波段和γ波段的相对功率降低。这种功率分布的病理模式通过NAc-DBS得到了改善。此外,我们发现,在OCD状态下,NAc中单胺类物质[多巴胺(DA)和5-羟色胺(5-HT)]和氨基酸[谷氨酸(Glu)和γ-氨基丁酸(GABA)]的局部水平升高,并且NAc中两种类型的DA受体的表达呈现相反的变化。这些异常可通过NAc-DBS逆转。这些发现为NAc在OCD病理生理学中的功能提供了更全面的理解,并为NAc-DBS的潜在作用提供了更详细的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e986/9845878/f513f3056fdd/fncel-16-1057887-g001.jpg

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