• Kazuhiro Kurokawa, Minoru Tsuji, Kohei Takahashi, Kazuya Miyagawa, Atsumi Mochida-Saito, and Hiroshi Takeda.
• Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
• Neuroscience. 2020 Oct 15; 446: 1-13.

AbstractLeukemia inhibitory factor (LIF) has been shown to be involved in myelination. The present study investigated whether LIF plays a significant role in the formation of stress adaptation using stress-adaptive and -maladaptive mice, and also attempted to confirm whether there was any difference in myelination between these animal models. A single exposure to restraint stress for 1 h induced a decrease in head-dipping behavior in the hole-board test. This stress response was not seen in mice that had been exposed to restraint stress for 1 h/day for 14 days, which is referred to as stress adaptation. In contrast, repeated exposure to restraint stress for 4 h/day for 14 days did not lead to the development of stress adaptation, and was still associated with a decrease in head-dipping behaviors. Under these conditions, LIF protein was found to be increased with astrocyte activation in the hippocampus of stress-adaptive mice, whereas no change was observed in stress-maladaptive mice. On the other hand, major myelin proteins including myelin-associated glycoprotein and myelin basic protein, as well as mature oligodendrocytes, were decreased in the hippocampus of stress-maladaptive, but not stress-adaptive, mice. Furthermore, while the levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) were increased in the hippocampus of stress-adaptive, this change did not occur in stress-maladaptive mice. Taken together, the present findings suggest that LIF, which may be derived from activated astrocytes, plays a critical role in the maintenance of hippocampal myelination via an ERK signaling pathway, and contributes to the development of stress adaptation.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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