Related Experiment Video
Updated: May 10, 2026
Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis
Published on: September 9, 2022
The anti-inflammatory effect of donepezil on experimental autoimmune encephalomyelitis in C57 BL/6 mice
Ying Jiang1, Yan Zou, Shaoqiong Chen
1Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
Abstract:
Donepezil is a potent and selective acetylcholinesterase inhibitor. It has been reported to restore cognitive performance in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) mice, an established model of MS. However, there are no reports about the anti-inflammatory effects of donepezil on EAE. In this study, the donepezil treatments on EAE mice were initiated at day 7 post immunization (7 p.i., subclinical periods, early donepezil treatment) and day 13 p.i. (clinical periods, late donepezil treatment) with the dosage of 1, 2 and 4 mg/kg/d respectively and the treatments persisted throughout the experiments. Blood-brain barrier (BBB) permeability was detected by Evan's blue content, the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, Akt and phosphorylated Akt (p-Akt) as well as nerve growth factor (NGF) and its precursor form (proNGF) in the brains of EAE mice were detected by Western blot, and the levels of interferon-γ and interleukin-4 in the splenocytes culture supernatants and brains of EAE mice were evaluated by ELISA. The results showed that the 2 mg/kg/d late donepezil treatment was the optimal dosage and could ameliorate clinical and pathological parameters, improve magnetic resonance imaging outcomes, reduce the permeability of BBB, inhibit the production of MMP-2 and MMP-9, modulate the expression of NGF and proNGF, increase Th2 bias and the phosphorylation of Akt in the brains of EAE mice. Our data suggested that the anti-inflammatory effects of donepezil may be a novel mechanism on treating EAE and provided further insights to understand the donepezil's neuroprotective activities in MS.
Insights
Donepezil demonstrates anti-inflammatory effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Late-stage treatment with donepezil ameliorates disease symptoms and reduces brain inflammation.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple Sclerosis (MS) is a demyelinating disease affecting the central nervous system.
- Donepezil, an acetylcholinesterase inhibitor, is known to improve cognitive function in MS patients.
- The anti-inflammatory effects of donepezil in MS models remain largely unexplored.
Purpose of the Study:
- To investigate the potential anti-inflammatory effects of donepezil in experimental autoimmune encephalomyelitis (EAE) mice.
- To determine the optimal dosage and timing for donepezil treatment in EAE.
- To elucidate the underlying mechanisms of donepezil's neuroprotective activity in MS.
Main Methods:
- EAE mice were treated with varying dosages of donepezil during early (subclinical) and late (clinical) disease stages.
- Blood-brain barrier (BBB) permeability was assessed using Evan's blue.
- Protein expression (MMP-2, MMP-9, Akt, p-Akt, NGF, proNGF) and cytokine levels (IFN-γ, IL-4) were analyzed via Western blot and ELISA.
Main Results:
- Late-stage treatment with 2 mg/kg/d donepezil was optimal, significantly improving clinical and pathological EAE outcomes.
- Donepezil treatment reduced BBB permeability, inhibited MMP-2 and MMP-9 production, and modulated NGF/proNGF expression.
- Treatment increased Th2 bias and Akt phosphorylation in the brains of EAE mice.
Conclusions:
- Donepezil exhibits significant anti-inflammatory and neuroprotective effects in EAE, suggesting a novel therapeutic mechanism.
- These findings provide further insight into donepezil's potential as a treatment for multiple sclerosis.
- Targeting acetylcholinesterase with donepezil may offer a new strategy for managing neuroinflammation in MS.
