Arbutin Improves Functional Recovery and Attenuates Glial Activation in Lysolecethin-Induced Demyelination Model in Rat Optic Chiasm

Abstract

Neuroinflammation, glial activation, and oxidative injury are the main pathological mechanisms of demyelination in multiple sclerosis (MS). Arbutin, a natural polyphenol compound, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has not been studied in the experimental animal models of MS. In the present study, the efficiency of arbutin on lysolecthin (LPC)-induced local demyelination model was investigated. Demyelination was induced by micro-injection of 2 μl LPC (1%) into the rat optic chiasm and the treated group received daily injection of arbutin (50 mg/kg, i.p) during 2 weeks. Visual-evoked potential (VEP) recordings were used to functionally assess the visual pathway. Gene expression analysis was done to evaluate the arbutin effect on the inflammatory, stress oxidative-related mediators, and myelin markers. The myelin-specific staining was performed to assess demyelination and GFAP staining as an astrocyte marker. We found that arbutin significantly reduced P1-latency of VEPs waves and demyelination at 7 and 14 days post-demyelination. Arbutin decreased inflammatory cytokines (IL-1B, IL-17, TNF-α) and iNOS mRNA expression level. In addition, the expression level of anti-inflammatory cytokine (IL-10) and antioxidant mediators (Nrf-2 and HO-1) was enhanced by arbutin treatment. Arbutin increased MBP and Olig2 expression levels in demyelination context. Finally, arbutin attenuated GFAP as an astrocyte marker. Finally, this study demonstrates that arbutin improves functional recovery and myelin repair in the demyelinated optic chiasm through attenuation of inflammation, astrocyte activation, and oxidative stress. These findings might open new promising avenues for treating demyelinating disorders such as multiple sclerosis.

Graphical abstract

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Abbreviations

GFAP:

Glial fibrillary acidic protein

HO-1:

Heme oxygenase-1

IL-1B:

Interleukin-1beta

IL-17:

Interleukin-17

IL-10:

Interleukin-10

iNOS:

Inducible nitric oxide synthase

LPC:

Lysophosphatidylcholine

MS:

Multiple sclerosis

MBP:

Myelin basic protein

Nrf-2:

Nuclear factor erythroid2-related factor-2

OPCs:

Oligodendrocyte precursor cells

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor alpha

VEP:

Visual-evoked potential

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Acknowledgments

This work was supported by a grant from the Deputy of Research and Technology (No. 9603818), Babol University of Medical Sciences, Babol, Iran and was performed as a part of a Medical doctor thesis in the Physiology Department at Babol University of Medical Sciences. The authors would like to appreciate the kind assistance and support of Dr. Mohammad Javan during the study. The authors are thankful to Mr. Saeed Maniati from Babol University of Medical Sciences for designing the graphical abstract.

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Contributions

Study design was done by Fereshteh Pourabdolhossein, Mahdi Pouramir, and Manuchehr Ashrafpour. Data collection was done by Forough Ebrahim-Tabar and Atena Nazari. Data analysis was done by Forough Ebrahim-Tabar, Atena Nazari and Fereshteh Pourabdolhossein. Manuscript preparation was done by Forough Ebrahim-Tabar and Fereshteh Pourabdolhossein. Final approval of the manuscript before submission was by Forough Ebrahim-Tabar, Fereshteh Pourabdolhossein, Atena Nazari, Mahdi Pouramir, and Manuchehr Ashrafpour.

Corresponding author

Correspondence to Fereshteh Pourabdolhossein.

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All experimental procedures were conducted based on the principles and procedures described in the National Institutes of Health guidelines for the care and use of laboratory animals and approved by the ethical committee of the Babol University of Medical Sciences (IR.MUBABOL.HRI.REC.1396.75).

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Highlights

• Arbutin improves functional recovery and myelin repair in demyelination model of the rat optic chiasm.

• Arbutin enhances OPC population and MBP expression in the rat demyelinated optic chiasm.

• Arbutin reduces the levels of inflammatory mediators and astrocytes activation in demyelination context.

• Arbutin increases the level of IL-10 and antioxidant gene markers in a LPC-induced demyelination model

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Ebrahim-Tabar, F., Nazari, A., Pouramir, M. et al. Arbutin Improves Functional Recovery and Attenuates Glial Activation in Lysolecethin-Induced Demyelination Model in Rat Optic Chiasm. Mol Neurobiol 57, 3228–3242 (2020). https://doi.org/10.1007/s12035-020-01962-x

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Keywords

  • Arbutin
  • Demyelination
  • Inflammation
  • Astrocyte activation
  • Oxidative stress