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加速高频重复经颅磁刺激诱导时间依赖性多巴胺能改变:一项对健康比格犬的DaTSCAN脑成像研究。

Accelerated high frequency rTMS induces time-dependent dopaminergic alterations: a DaTSCAN brain imaging study in healthy beagle dogs.

作者信息

Xu Yangfeng, Peremans Kathelijne, Salden Sofie, Audenaert Kurt, Dobbeleir Andre, Van Eeckhaut Ann, De Bundel Dimitri, Saunders Jimmy H, Baeken Chris

机构信息

Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, Ghent, Belgium.

Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

出版信息

Front Vet Sci. 2023 May 16;10:1154596. doi: 10.3389/fvets.2023.1154596. eCollection 2023.

Abstract

AIM

The neurobiological effects of repetitive transcranial magnetic stimulation are believed to run in part through the dopaminergic system. Accelerated high frequency rTMS (aHF-rTMS), a new form of stimuli delivery, is currently being tested for its usefulness in treating human and canine mental disorders. However, the short-and long-term neurobiological effects are still unclear, including the effects on the dopaminergic system. In aHF-rTMS, multiple sessions are delivered within 1 day instead of one session per day, not only to accelerate the time to response but also to increase clinical efficacy. To gain more insight into the neurobiology of aHF-rTMS, we investigated whether applying five sessions in 1 day has direct and/or delayed effects on the dopamine transporter (DAT), and on dopamine metabolites of cerebrospinal fluid (CSF) in beagles.

MATERIALS AND METHODS

Thirteen beagles were randomly divided into two groups: five active stimulation sessions ( = 9), and 5 sham stimulation sessions ( = 4). Using DaTSCAN, DAT binding indices (BI) were obtained at baseline, after 1 day, 1 month, and 3 months post stimulation. CSF samples were collected after each scan.

RESULTS

Active aHF-rTMS significantly reduced striatal DAT BI 1 day post-active stimulation session ( < 0.01), and the effect lasted to 1 month ( < 0.01). No significant DAT BI change was found in sham group. No significant changes in dopamine metabolites of CSF were found.

CONCLUSION

Although no significant effects on CSF dopamine metabolites were observed, five sessions of active aHF-rTMS significantly decreased striatal DAT BI after 1 day and up to 1 month post stimulation, indicating immediate and delayed effects on the brain dopaminergic system. Our findings in healthy beagles further substantiate the assumption that (a)HF-rTMS affects the brain dopaminergic system and it may pave the way to apply (a)HF-rTMS treatment in behaviorally disturbed dogs.

摘要

目的

重复经颅磁刺激的神经生物学效应被认为部分通过多巴胺能系统起作用。加速高频重复经颅磁刺激(aHF-rTMS)是一种新的刺激传递形式,目前正在测试其在治疗人类和犬类精神障碍方面的有效性。然而,其短期和长期神经生物学效应仍不清楚,包括对多巴胺能系统的影响。在aHF-rTMS中,一天内进行多次治疗而非每天一次,不仅是为了加快起效时间,也是为了提高临床疗效。为了更深入了解aHF-rTMS的神经生物学机制,我们研究了在一天内进行五次治疗对比格犬多巴胺转运体(DAT)以及脑脊液(CSF)中多巴胺代谢产物是否有直接和/或延迟效应。

材料与方法

13只比格犬随机分为两组:五次主动刺激治疗组(n = 9)和五次假刺激治疗组(n = 4)。使用DaTSCAN,在刺激前基线、刺激后1天、1个月和3个月时获取DAT结合指数(BI)。每次扫描后收集脑脊液样本。

结果

主动aHF-rTMS治疗后1天,纹状体DAT BI显著降低(P < 0.01),且该效应持续至1个月(P < 0.01)。假刺激组未发现DAT BI有显著变化。脑脊液中多巴胺代谢产物未发现显著变化。

结论

虽然未观察到对脑脊液多巴胺代谢产物有显著影响,但五次主动aHF-rTMS治疗在刺激后1天及长达1个月时显著降低了纹状体DAT BI,表明对脑多巴胺能系统有即时和延迟效应。我们在健康比格犬中的研究结果进一步证实了(a)HF-rTMS影响脑多巴胺能系统这一假设,并且可能为在行为紊乱犬中应用(a)HF-rTMS治疗铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59bf/10228829/9fe0ee3abe78/fvets-10-1154596-g001.jpg

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