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

First Author  Makinodan M Year  2016
Journal  FASEB J Volume  30
Issue  12 Pages  4267-4274
PubMed ID  27613805 Mgi Jnum  J:268517
Mgi Id  MGI:6268096 Doi  10.1096/fj.201600537R
Citation  Makinodan M, et al. (2016) Social isolation impairs remyelination in mice through modulation of IL-6. FASEB J 30(12):4267-4274
abstractText  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 mug 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 mug 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.
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