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经颅直流电刺激改善注意缺陷多动障碍动物模型的长期记忆缺陷,并调节氧化和炎症参数。

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

机构信息

Post-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Laboratory of Pain Pharmacology and Neuromodulation: Pre Clinical Studies - Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Biochemistry Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

出版信息

Brain Stimul. 2018 Jul-Aug;11(4):743-751. doi: 10.1016/j.brs.2018.04.001. Epub 2018 Apr 5.

Abstract

BACKGROUND

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear.

OBJECTIVE/HYPOTHESIS: We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS.

METHODS

Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated.

RESULTS

TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines.

CONCLUSION

TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored.

摘要

背景

经颅直流电刺激(tDCS)是一种调节神经元活动的技术,已被提议作为治疗注意力缺陷多动障碍(ADHD)症状的潜在工具。尽管初步研究已经证明了其疗效,但作用机制仍不清楚。

目的/假设:我们评估了 tDCS 对与 ADHD 病理生理学相关的行为(工作和长期记忆)和神经化学(氧化和炎症参数)结果的影响。我们使用了最广泛接受的 ADHD 动物模型:自发性高血压大鼠(SHR)。所选的行为结果在 ADHD 患者和动物模型中均发生改变,并且与 tDCS 的拟议作用机制有关。

方法

成年雄性 SHR 和它们的对照 Wistar Kyoto 大鼠(WKY)接受双极 tDCS 或假刺激 20 分钟,连续 8 天。评估工作记忆、长期记忆和神经化学结果。

结果

tDCS 改善了 SHR 存在的长期记忆缺陷。未观察到工作记忆表现的变化。在海马体中,tDCS 增加了 SHR 中活性氧的产生和两种菌株中抗氧化分子谷胱甘肽的水平。tDCS 还通过下调促炎细胞因子调节了 WKY 大脑中的炎症反应。

结论

tDCS 对行为和神经化学结果具有特定的、针对特定品系的显著影响。SHR 的长期记忆改善可能表明 tDCS 在 ADHD 中的治疗作用,而这种作用似乎不是通过炎症标志物介导的。此外,tDCS 后 WKY 大脑中观察到的抗炎作用需要进一步探索。

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