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 language | English |
|---|---|
| Journal | CNS Drugs |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2019 |
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ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health
- Pharmacology (medical)
Cite this
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 journal › Article
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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.
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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 -