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益生菌补充剂通过增加神经营养因子和减少促炎细胞因子来减轻 WAG/Rij 大鼠的失神发作以及焦虑和抑郁样行为。

Probiotic supplementation alleviates absence seizures and anxiety- and depression-like behavior in WAG/Rij rat by increasing neurotrophic factors and decreasing proinflammatory cytokines.

机构信息

Department of Physiology, Faculty of Medicine, University of Tokat Gaziosmanpasa, Tokat, Turkey.

Department of Biology, Faculty of Science and Literature, University of Erciyes, Kayseri, Turkey.

出版信息

Epilepsy Behav. 2022 Mar;128:108588. doi: 10.1016/j.yebeh.2022.108588. Epub 2022 Feb 10.

Abstract

AIM

Epilepsy is one of the most common chronic brain disorders that affect millions of people worldwide. In the present study, we investigated the effects of probiotic supplementation on absence epilepsy and anxiety-and depression-like behavior in WAG/Rij rats.

MATERIAL AND METHOD

Fourteen male WAG/Rij rats (absence-epileptic) and seven male Wistar rats (nonepileptic) were used. The effects of probiotic VSL#3 (12.86 bn living bacteria/kg/day for 30 day/gavage) on absence seizures, and related psychiatric comorbidities were evaluated in WAG/Rij rats. Anxiety-like behavior was evaluated by the open-field test and depression-like behavior by the forced swimming test. In addition, the brain tissues of rats were evaluated histopathologically for nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], SRY sex-determining region Y-box 2 [SOX2] and biochemically for nitric oxide [NO], tumor necrosis factor-alpha [TNF-α] ,and Interleukin-6 [IL-6].

RESULTS

Compared to Wistar rats, WAG/Rij rats exhibited anxiety- and depression-like behavior, and had lower BDNF, NGF and SOX2 immunoreactivity, and higher TNF-α, IL-6 levels in brain tissue. VSL#3 supplementation reduced the duration and number of spike-wave discharges (SWDs) and exhibited anxiolytic or anti-depressive effect. VSL#3 supplement also increased the NGF immunoreactivity while decreasing IL-6, TNF-α and NO levels in WAG/Rij rat brain.

CONCLUSION

The findings of the present study showed that neurotrophins, SOX2 deficiency, and pro-inflammatory cytokines may play a role in the pathogenesis of absence epilepsy. Our data support the hypothesis that the probiotics have anti-inflammatory effect. The present study is the first to show the positive effects of probiotic bacteria on absence seizures and anxiety- and depression-like behavior.

摘要

目的

癫痫是一种最常见的慢性脑部疾病,影响着全球数以百万计的人。本研究旨在探讨益生菌补充对 WAG/Rij 大鼠失神癫痫和焦虑-抑郁样行为的影响。

材料与方法

本研究使用了 14 只雄性 WAG/Rij 大鼠(失神癫痫)和 7 只雄性 Wistar 大鼠(无癫痫)。通过对 WAG/Rij 大鼠进行灌胃 30 天(每天 12.86 亿活细菌/kg)VSL#3 益生菌治疗,评估益生菌对失神发作的影响及相关精神共病。通过旷场试验评估焦虑样行为,通过强迫游泳试验评估抑郁样行为。此外,还对大鼠脑组织进行神经生长因子[NGF]、脑源性神经营养因子[BDNF]、性别决定区 Y 框 2 [SOX2]的组织病理学评估和一氧化氮[NO]、肿瘤坏死因子-α[TNF-α]、白细胞介素-6 [IL-6]的生化评估。

结果

与 Wistar 大鼠相比,WAG/Rij 大鼠表现出焦虑-抑郁样行为,大脑组织中 BDNF、NGF 和 SOX2 免疫反应性降低,TNF-α、IL-6 水平升高。VSL#3 补充减少了尖波-慢波放电(SWD)的持续时间和数量,并表现出抗焦虑或抗抑郁作用。VSL#3 补充还增加了 WAG/Rij 大鼠大脑中的 NGF 免疫反应性,同时降低了 IL-6、TNF-α 和 NO 水平。

结论

本研究结果表明,神经营养因子、SOX2 缺乏和促炎细胞因子可能在失神癫痫的发病机制中起作用。我们的数据支持益生菌具有抗炎作用的假设。本研究首次表明益生菌对失神发作和焦虑-抑郁样行为有积极影响。

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