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口服 D-天冬氨酸增强进行性多发性硬化症的突触可塑性储备。

Oral D-Aspartate enhances synaptic plasticity reserve in progressive multiple sclerosis.

机构信息

Multiple Sclerosis Clinical & Research Center, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, The Second University of Naples, Caserta, Italy/ Laboratory of Behavioral Neuroscience, CEINGE -Biotecnologie Avanzate, Naples, Italy.

出版信息

Mult Scler. 2020 Mar;26(3):304-311. doi: 10.1177/1352458519828294. Epub 2019 Feb 7.

Abstract

BACKGROUND

Synaptic plasticity reserve correlates with clinical recovery after a relapse in relapsing-remitting forms of multiple sclerosis (MS) and is significantly compromised in patients with progressive forms of MS. These findings suggest that progression of disability in MS is linked to reduced synaptic plasticity reserve. D-Aspartate, an endogenous aminoacid approved for the use in humans as a dietary supplement, enhances synaptic plasticity in mice.

OBJECTIVE

To test whether D-Aspartate oral intake increases synaptic plasticity reserve in progressive MS patients.

METHODS

A total of 31 patients affected by a progressive form of MS received either single oral daily doses of D-Aspartate 2660 mg or placebo for 4 weeks. Synaptic plasticity reserve and trans-synaptic cortical excitability were measured through transcranial magnetic stimulation (TMS) protocols before and after D-Aspartate.

RESULTS

Both TMS-induced long-term potentiation (LTP), intracortical facilitation (ICF) and short-interval ICF increased after 2 and 4 weeks of D-Aspartate but not after placebo, suggesting an enhancement of synaptic plasticity reserve and increased trans-synaptic glutamatergic transmission.

CONCLUSION

Daily oral D-Aspartate 2660 mg for 4 weeks enhances synaptic plasticity reserve in patients with progressive MS, opening the path to further studies assessing its clinical effects on disability progression.

摘要

背景

突触可塑性储备与复发缓解型多发性硬化症(MS)复发后的临床恢复相关,在进展型 MS 患者中显著受损。这些发现表明,MS 残疾的进展与突触可塑性储备减少有关。D-天冬氨酸是一种内源性氨基酸,已被批准作为膳食补充剂用于人类,可增强小鼠的突触可塑性。

目的

测试 D-天冬氨酸口服摄入是否会增加进展型 MS 患者的突触可塑性储备。

方法

共有 31 名患有进展型 MS 的患者接受了单次口服 D-天冬氨酸 2660mg 或安慰剂治疗,为期 4 周。在接受 D-天冬氨酸或安慰剂治疗前后,通过经颅磁刺激(TMS)方案测量突触可塑性储备和跨突触皮质兴奋性。

结果

D-天冬氨酸治疗 2 周和 4 周后,TMS 诱导的长时程增强(LTP)、皮质内易化(ICF)和短间隔 ICF 均增加,而安慰剂组则没有,提示突触可塑性储备增强和跨突触谷氨酸能传递增加。

结论

每日口服 D-天冬氨酸 2660mg 治疗 4 周可增强进展型 MS 患者的突触可塑性储备,为进一步评估其对残疾进展的临床效果的研究铺平了道路。

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