Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis

Xiaoli Guo; Kazuaki Nakamura; Kuniko Kohyama; Chikako Harada; Heather A. Behanna; D. Martin Watterson; Yoh Matsumoto; Takayuki Harada

doi:10.1016/j.neures.2007.08.014

Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis

Xiaoli Guo, Kazuaki Nakamura, Kuniko Kohyama, Chikako Harada, Heather A. Behanna, D. Martin Watterson, Yoh Matsumoto, Takayuki Harada^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

Activated microglia and astrocytes have been implicated in the course of multiple sclerosis (MS) and its animal model: experimental autoimmune encephalomyelitis (EAE). MW01-5-188WH is a novel drug that selectively inhibits glial activation in the central nervous system (CNS). We report here that MW01-5-188WH is effective to ameliorate the severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Daily oral administration of MW01-5-188WH at 5 mg/kg body weight reduced the clinical scores of EAE mice while having no influence on the disease incidence or animal mortality. Pathological examination revealed reduced numbers of microglia and astrocytes in the spinal cord of MW01-5-188WH-treated EAE mice. Moreover, MW01-5-188WH suppressed the release of key chemokines, which are involved in MS pathology, from cultured microglia and astrocytes. Taken together, our results indicate that treatments that suppress the activation of microglia and astrocytes should be pursued in future research for their potential as avenues for the treatment of MS.

Original language	English (US)
Pages (from-to)	457-466
Number of pages	10
Journal	Neuroscience Research
Volume	59
Issue number	4
DOIs	https://doi.org/10.1016/j.neures.2007.08.014
State	Published - Dec 2007

Funding

We thank Drs. K. Ohsawa, Y. Nakamura, and S. Kohsaka for their advice on microglia cell culture. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (CH and TH), Naito Foundation and Uehara Memorial Foundation (TH). CH was supported by the Japan Society for the Promotion of Science for Young Scientists.

Keywords

Astrocytes
Chemokines
Experimental autoimmune encephalomyelitis
Glial activation
MW01-5-188WH
Microglia
Mouse
Spinal cord

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neures.2007.08.014

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title = "Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis",

abstract = "Activated microglia and astrocytes have been implicated in the course of multiple sclerosis (MS) and its animal model: experimental autoimmune encephalomyelitis (EAE). MW01-5-188WH is a novel drug that selectively inhibits glial activation in the central nervous system (CNS). We report here that MW01-5-188WH is effective to ameliorate the severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Daily oral administration of MW01-5-188WH at 5 mg/kg body weight reduced the clinical scores of EAE mice while having no influence on the disease incidence or animal mortality. Pathological examination revealed reduced numbers of microglia and astrocytes in the spinal cord of MW01-5-188WH-treated EAE mice. Moreover, MW01-5-188WH suppressed the release of key chemokines, which are involved in MS pathology, from cultured microglia and astrocytes. Taken together, our results indicate that treatments that suppress the activation of microglia and astrocytes should be pursued in future research for their potential as avenues for the treatment of MS.",

keywords = "Astrocytes, Chemokines, Experimental autoimmune encephalomyelitis, Glial activation, MW01-5-188WH, Microglia, Mouse, Spinal cord",

author = "Xiaoli Guo and Kazuaki Nakamura and Kuniko Kohyama and Chikako Harada and Behanna, {Heather A.} and Watterson, {D. Martin} and Yoh Matsumoto and Takayuki Harada",

note = "Funding Information: We thank Drs. K. Ohsawa, Y. Nakamura, and S. Kohsaka for their advice on microglia cell culture. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (CH and TH), Naito Foundation and Uehara Memorial Foundation (TH). CH was supported by the Japan Society for the Promotion of Science for Young Scientists.",

year = "2007",

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doi = "10.1016/j.neures.2007.08.014",

language = "English (US)",

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AU - Guo, Xiaoli

AU - Nakamura, Kazuaki

AU - Kohyama, Kuniko

AU - Harada, Chikako

AU - Behanna, Heather A.

AU - Watterson, D. Martin

AU - Matsumoto, Yoh

AU - Harada, Takayuki

N1 - Funding Information: We thank Drs. K. Ohsawa, Y. Nakamura, and S. Kohsaka for their advice on microglia cell culture. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (CH and TH), Naito Foundation and Uehara Memorial Foundation (TH). CH was supported by the Japan Society for the Promotion of Science for Young Scientists.

PY - 2007/12

Y1 - 2007/12

N2 - Activated microglia and astrocytes have been implicated in the course of multiple sclerosis (MS) and its animal model: experimental autoimmune encephalomyelitis (EAE). MW01-5-188WH is a novel drug that selectively inhibits glial activation in the central nervous system (CNS). We report here that MW01-5-188WH is effective to ameliorate the severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Daily oral administration of MW01-5-188WH at 5 mg/kg body weight reduced the clinical scores of EAE mice while having no influence on the disease incidence or animal mortality. Pathological examination revealed reduced numbers of microglia and astrocytes in the spinal cord of MW01-5-188WH-treated EAE mice. Moreover, MW01-5-188WH suppressed the release of key chemokines, which are involved in MS pathology, from cultured microglia and astrocytes. Taken together, our results indicate that treatments that suppress the activation of microglia and astrocytes should be pursued in future research for their potential as avenues for the treatment of MS.

AB - Activated microglia and astrocytes have been implicated in the course of multiple sclerosis (MS) and its animal model: experimental autoimmune encephalomyelitis (EAE). MW01-5-188WH is a novel drug that selectively inhibits glial activation in the central nervous system (CNS). We report here that MW01-5-188WH is effective to ameliorate the severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Daily oral administration of MW01-5-188WH at 5 mg/kg body weight reduced the clinical scores of EAE mice while having no influence on the disease incidence or animal mortality. Pathological examination revealed reduced numbers of microglia and astrocytes in the spinal cord of MW01-5-188WH-treated EAE mice. Moreover, MW01-5-188WH suppressed the release of key chemokines, which are involved in MS pathology, from cultured microglia and astrocytes. Taken together, our results indicate that treatments that suppress the activation of microglia and astrocytes should be pursued in future research for their potential as avenues for the treatment of MS.

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Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis

Abstract

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Keywords

ASJC Scopus subject areas

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