Social isolation impairs remyelination in mice through modulation of IL-6.
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.
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan; mmm@naramed-u.ac.jp.
Manabu
M
Makinodan
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Daisuke
D
Ikawa
Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan; and.
Yuki
Y
Miyamoto
Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan; and.
Junji
J
Yamauchi
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Kazuhiko
K
Yamamuro
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Yasunori
Y
Yamashita
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Michihiro
M
Toritsuka
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Sohei
S
Kimoto
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Kazuki
K
Okumura
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Takahira
T
Yamauchi
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Shin-Ichi
SI
Fukami
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Hiroki
H
Yoshino
Department of Anatomy and Neuroscience, Nara Medical University School of Medicine, Nara, Japan.
Akio
A
Wanaka
Department of Psychiatry, Nara Medical University School of Medicine, Nara, Japan.
Toshifumi
T
Kishimoto
D000818:Animals; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D012934:Social Isolation
D015850:Interleukin-6; C577686:interleukin-6, mouse; D003471:Cuprizone
cytokines; multiple sclerosis; oligodendrocyte; prefrontal cortex; social experience