論文

査読有り 国際誌
2016年12月

Social isolation impairs remyelination in mice through modulation of IL-6.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • Manabu Makinodan
  • ,
  • Daisuke Ikawa
  • ,
  • Yuki Miyamoto
  • ,
  • Junji Yamauchi
  • ,
  • Kazuhiko Yamamuro
  • ,
  • Yasunori Yamashita
  • ,
  • Michihiro Toritsuka
  • ,
  • Sohei Kimoto
  • ,
  • Kazuki Okumura
  • ,
  • Takahira Yamauchi
  • ,
  • Shin-Ichi Fukami
  • ,
  • Hiroki Yoshino
  • ,
  • Akio Wanaka
  • ,
  • Toshifumi Kishimoto

30
12
開始ページ
4267
終了ページ
4274
記述言語
英語
掲載種別
DOI
10.1096/fj.201600537R

Recent studies have revealed that social experience affects myelination. These findings have important implications for disorders that feature abnormal myelination, such as multiple sclerosis (MS), as previous studies have shown that psychosocial stress exacerbates the pathobiology of MS. However, most studies have focused on psychosocial stress during the demyelination phase of MS and have not investigated the effects of social experience on remyelination. Thus, the current study sought to determine whether social experience can alter remyelination after myelin depletion. Myelin in the mouse medial prefrontal cortex was depleted with cuprizone, and the effects of subsequent social isolation on remyelination were evaluated. Remyelination was severely impaired in socially isolated mice. Social isolation also increased IL-6 levels in the medial prefrontal cortex, and administration of an IL-6 inhibitor (ND50 = 0.01-0.03 μg for 0.25 ng/ml IL-6) ameliorated remyelination impairments. Consistent with this result, IL-6 administration (ED50 = 0.02-0.06 ng/ml) disturbed remyelination. In addition, neuron-oligodendrocyte coculture experiments showed that IL-6 treatment (ED50 ≤ 0.02 ng/ml) markedly impeded myelination, which was recovered with IL-6 inhibitor administration (ND50 = 0.01-0.03 μg for 0.25 ng/ml IL-6). This study provides the first direct evidence, to our knowledge, that social experience influences remyelination via modulation of IL-6 expression. These findings indicate that psychosocial stress may disturb remyelination through regulation of IL-6 expression in patients with such demyelinating diseases that involve remyelination as MS.-Makinodan, M., Ikawa, D., Miyamoto, Y., Yamauchi, J., Yamamuro, K., Yamashita, Y., Toritsuka, M., Kimoto, S., Okumura, K., Yamauchi, T., Fukami, S., Yoshino, H., Wanaka, A., Kishimoto, T. Social isolation impairs remyelination in mice through modulation of IL-6.

リンク情報
DOI
https://doi.org/10.1096/fj.201600537R
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27613805