Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis

Carolina Gabri Nicoletti, Doriana Landi, Fabrizia Monteleone, Giorgia Mataluni, Maria Albanese, Benedetta Lauretti, Camilla Rocchi, Ilaria Simonelli, Laura Boffa, Fabio Buttari, Nicola Biagio Mercuri, Diego Centonze, Girolama Alessandra Marfia

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalCNS Drugs
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Cholinergic Agents
Multiple Sclerosis
Therapeutics
Blood Pressure
Relapsing-Remitting Multiple Sclerosis
Neuronal Plasticity
Aptitude
Nicotinic Receptors
Bradycardia
Dimethyl Fumarate
Acetylcholine
Reflex
Healthy Volunteers
Anti-Inflammatory Agents
Animal Models
Antioxidants
Inhibition (Psychology)

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Nicoletti, C. G., Landi, D., Monteleone, F., Mataluni, G., Albanese, M., Lauretti, B., ... Marfia, G. A. (Accepted/In press). Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis. CNS Drugs. https://doi.org/10.1007/s40263-019-00676-6

Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis. / Nicoletti, Carolina Gabri; Landi, Doriana; Monteleone, Fabrizia; Mataluni, Giorgia; Albanese, Maria; Lauretti, Benedetta; Rocchi, Camilla; Simonelli, Ilaria; Boffa, Laura; Buttari, Fabio; Mercuri, Nicola Biagio; Centonze, Diego; Marfia, Girolama Alessandra.

In: CNS Drugs, 01.01.2019.

Research output: Contribution to journalArticle

Nicoletti, CG, Landi, D, Monteleone, F, Mataluni, G, Albanese, M, Lauretti, B, Rocchi, C, Simonelli, I, Boffa, L, Buttari, F, Mercuri, NB, Centonze, D & Marfia, GA 2019, 'Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis', CNS Drugs. https://doi.org/10.1007/s40263-019-00676-6
Nicoletti CG, Landi D, Monteleone F, Mataluni G, Albanese M, Lauretti B et al. Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis. CNS Drugs. 2019 Jan 1. https://doi.org/10.1007/s40263-019-00676-6
Nicoletti, Carolina Gabri ; Landi, Doriana ; Monteleone, Fabrizia ; Mataluni, Giorgia ; Albanese, Maria ; Lauretti, Benedetta ; Rocchi, Camilla ; Simonelli, Ilaria ; Boffa, Laura ; Buttari, Fabio ; Mercuri, Nicola Biagio ; Centonze, Diego ; Marfia, Girolama Alessandra. / Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis. In: CNS Drugs. 2019.
@article{6ab54cb70260401182805b75523fc5cc,
title = "Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis",
abstract = "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.",
author = "Nicoletti, {Carolina Gabri} and Doriana Landi and Fabrizia Monteleone and Giorgia Mataluni and Maria Albanese and Benedetta Lauretti and Camilla Rocchi and Ilaria Simonelli and Laura Boffa and Fabio Buttari and Mercuri, {Nicola Biagio} and Diego Centonze and Marfia, {Girolama Alessandra}",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s40263-019-00676-6",
language = "English",
journal = "CNS Drugs",
issn = "1172-7047",
publisher = "Adis International Ltd",

}

TY - JOUR

T1 - Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis

AU - Nicoletti, Carolina Gabri

AU - Landi, Doriana

AU - Monteleone, Fabrizia

AU - Mataluni, Giorgia

AU - Albanese, Maria

AU - Lauretti, Benedetta

AU - Rocchi, Camilla

AU - Simonelli, Ilaria

AU - Boffa, Laura

AU - Buttari, Fabio

AU - Mercuri, Nicola Biagio

AU - Centonze, Diego

AU - Marfia, Girolama Alessandra

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85074407276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074407276&partnerID=8YFLogxK

U2 - 10.1007/s40263-019-00676-6

DO - 10.1007/s40263-019-00676-6

M3 - Article

C2 - 31650471

AN - SCOPUS:85074407276

JO - CNS Drugs

JF - CNS Drugs

SN - 1172-7047

ER -