Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis
Xiaoli Guo1, Chikako Harada, Kazuhiko Namekata
1Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan.
Purpose:
To assess the effects of spermidine on the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), with a focus on optic neuritis often associated with MS and EAE.
Methods:
Myelin oligodendrocyte glycoprotein-induced EAE mice were administered with or without spermidine at 30 mM in drinking water for 25 days. Clinical signs of EAE were scored daily, and visual functions were measured by multifocal electroretinograms. Histopathology analysis of the spinal cord and optic nerve was performed after mice were killed on day 25. Hydrogen peroxide (H(2)O(2)) was detected using the probe 2'-7' dichlorofluorescein diacetate (DCFDA) in the optic nerve. The effect of spermidine on H(2)O(2)-induced retinal ganglion cell apoptosis was investigated by lactate dehydrogenase assay.
Results:
Daily clinical scoring revealed that the severity of EAE was significantly attenuated in the spermidine-treated group, which was confirmed by milder demyelination and improved axon survival in the spinal cord of spermidine-treated mice. Visual functions were significantly improved in spermidine-treated mice compared with vehicle-treated mice. Spermidine treatment ameliorated the extent of demyelination in the optic nerve and prevented cell loss in the retinal ganglion cell layer. Furthermore, fewer DCFDA-labeled cells were found in the optic nerve in the spermidine-treated EAE mice, and in vitro analysis revealed that spermidine reduced H(2)O(2)-induced retinal ganglion cell apoptosis, suggesting that spermidine alleviated the severities of EAE, particularly of optic neuritis, by acting as an antioxidant.
Conclusions:
The results from this study suggest that oral spermidine administration could be a useful treatment for MS.
Insights
Spermidine treatment significantly reduced the severity of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). This antioxidant compound also improved visual function and protected against optic neuritis, suggesting potential as an MS therapy.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system.
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for studying MS pathogenesis and therapeutic strategies.
- Optic neuritis is a common and often debilitating symptom in MS and EAE, affecting visual function.
Purpose of the Study:
- To investigate the therapeutic potential of spermidine in mitigating the clinical and pathological manifestations of EAE.
- To specifically evaluate the impact of spermidine on optic neuritis, a hallmark of MS and EAE.
- To explore the underlying mechanisms, including antioxidant effects, of spermidine's action in EAE.
Main Methods:
- EAE was induced in mice using myelin oligodendrocyte glycoprotein.
- Spermidine was administered orally via drinking water for 25 days.
- Clinical EAE scores, visual function (multifocal electroretinograms), spinal cord and optic nerve histopathology, and oxidative stress markers were assessed.
Main Results:
- Spermidine treatment significantly attenuated EAE clinical severity, reducing demyelination and improving axon survival.
- Mice receiving spermidine exhibited improved visual function and reduced optic nerve demyelination.
- Spermidine demonstrated antioxidant properties by reducing hydrogen peroxide-induced retinal ganglion cell apoptosis and oxidative stress in the optic nerve.
Conclusions:
- Oral spermidine administration effectively ameliorates EAE severity and associated optic neuritis in a preclinical model.
- Spermidine's antioxidant activity contributes to its neuroprotective effects in EAE.
- Spermidine shows promise as a potential therapeutic agent for managing multiple sclerosis.
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