BACKGROUND Dimethyl fumarate (DMF) exerts anti-inflammatory effects in multiple sclerosis by activating the Nrf2 antioxidant pathway, which is also stimulated by acetylcholine via alpha-7 nicotinic acetylcholine receptors. In animal models, Nrf2 potentiates cholinergic synaptic plasticity. OBJECTIVE The aim of this study was to test whether treatment with DMF modulates cholinergic pathways in relapsing-remitting multiple sclerosis (RRMS). METHODS Patients starting DMF (20) or IFN-β 1a (20) and healthy subjects (20) were enrolled. Short-latency afferent inhibition (SAI), which is a transcranial stimulation measure of central cholinergic transmission, was recorded in patients and controls at baseline and, in patients only, after 6 months of treatment. Patients treated with DMF also underwent autonomic function testing to further explore peripheral and central cholinergic tone. RESULTS At baseline, SAI was similar in patients and in controls (p = 0.983). Treatment with DMF significantly increased SAI (p = 0.01), while IFNβ had no effect (p = 0.80). In the cold face test, DMF treatment also increased reflex bradycardia (p = 0.013), and reduced diastolic blood pressure variation (p = 0.010), further indicating its ability to stimulate cholinergic transmission. CONCLUSIONS Treatment of MS patients with DMF results in increased cholinergic stimulation, with possible implications for neuroinflammation and neuroprotection.

中文翻译：

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富马酸二甲酯治疗可增强多发性硬化症的胆碱能传递。

背景技术富马酸二甲酯（DMF）通过激活Nrf2抗氧化剂途径在多发性硬化症中发挥抗炎作用，该抗氧化剂途径也被乙酰胆碱经由α-7烟碱型乙酰胆碱受体刺激。在动物模型中，Nrf2增强胆碱能突触可塑性。目的本研究的目的是检验DMF治疗是否可调节复发缓解型多发性硬化症（RRMS）中的胆碱能途径。方法纳入开始DMF（20）或IFN-β1a（20）和健康受试者（20）的患者。在基线时以及仅在患者治疗6个月后，在患者和对照组中记录了短时延缓入抑制（SAI），这是对中央胆碱能传递的经颅刺激测量。接受DMF治疗的患者还接受了自主功能测试，以进一步探索外周和中枢胆碱能的语气。结果基线时，患者和对照组的SAI相似（p = 0.983）。用DMF进行治疗可显着提高SAI（p = 0.01），而IFNβ无作用（p = 0.80）。在冷脸试验中，DMF治疗还增加了反射性心动过缓（p = 0.013），并降低了舒张压变化（p = 0.010），进一步表明了其刺激胆碱能传播的能力。结论MS DMF患者的治疗可增加胆碱能刺激，可能对神经炎症和神经保护产生影响。而IFNβ无作用（p = 0.80）。在冷脸试验中，DMF治疗还增加了反射性心动过缓（p = 0.013），并降低了舒张压变化（p = 0.010），进一步表明了其刺激胆碱能传播的能力。结论MS DMF患者的治疗可增加胆碱能刺激，可能对神经炎症和神经保护产生影响。而IFNβ无作用（p = 0.80）。在冷脸试验中，DMF治疗还增加了反射性心动过缓（p = 0.013），并降低了舒张压变化（p = 0.010），进一步表明了其刺激胆碱能传播的能力。结论MS DMF患者的治疗可增加胆碱能刺激，可能对神经炎症和神经保护产生影响。