Related Experiment Video
Updated: May 11, 2026
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Minocycline reduces remyelination by suppressing ciliary neurotrophic factor expression after cuprizone-induced
Tatsuhide Tanaka1, Koichi Murakami, Yoshio Bando
1Department of Functional Anatomy and Neuroscience, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Abstract:
Remyelination is disrupted in demyelinating diseases such as multiple sclerosis, but the underlying pathogenetic mechanisms are unclear. In this study, we employed the murine cuprizone model of demyelination, in which remyelination occurs after removal of the toxin from the diet, to examine the cellular and molecular changes during demyelination and remyelination. Microglia accumulated in the corpus callosum during weeks 2-4 of the cuprizone diet, and these cells remained activated 2 weeks after the change to the normal diet. To examine the role of microglia in remyelination, mice were treated with minocycline to inactivate these cells after cuprizone-induced demyelination. Minocycline treatment reduced the number of CC1-positive oligodendrocytes, as well as levels of myelin basic protein (MBP) and CNPase in the remyelination phase. The expression of CNTF mRNA in the corpus callosum increased after 4 weeks on the cuprizone diet and remained high 2 weeks after the change to the normal diet. Minocycline suppressed CNTF expression during the remyelination phase on the normal diet. Primary culture experiments showed that CNTF was produced by microglia in addition to astrocytes. In vitro, CNTF directly affected the differentiation of oligodendrocytic cells. These findings suggest that minocycline reduces remyelination by suppressing CNTF expression by microglia after cuprizone-induced demyelination.
Insights
Minocycline impairs remyelination in a mouse model of demyelination by suppressing microglial Ciliary Neurotrophic Factor (CNTF) production. This suggests microglia play a key role in the remyelination process.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Demyelinating diseases like multiple sclerosis exhibit disrupted remyelination.
- The precise pathogenetic mechanisms underlying these disruptions remain unclear.
Purpose of the Study:
- To investigate cellular and molecular changes during demyelination and remyelination using the cuprizone model.
- To elucidate the role of microglia in the remyelination process.
Main Methods:
- Utilized the murine cuprizone model of demyelination.
- Administered minocycline to inactivate microglia during the remyelination phase.
- Assessed oligodendrocyte numbers (CC1-positive), myelin basic protein (MBP), and CNPase levels.
- Measured Ciliary Neurotrophic Factor (CNTF) mRNA expression.
- Conducted primary cell cultures to examine CNTF production and its effect on oligodendrocytes.
Main Results:
- Microglia accumulated and remained activated in the corpus callosum during and after cuprizone exposure.
- Minocycline treatment reduced oligodendrocyte numbers and myelin markers during remyelination.
- CNTF mRNA expression increased during demyelination and persisted into the remyelination phase.
- Minocycline suppressed CNTF expression during remyelination.
- CNTF is produced by both microglia and astrocytes and directly influences oligodendrocyte differentiation.
Conclusions:
- Minocycline treatment appears to reduce remyelination by inhibiting microglial CNTF expression.
- Microglia-derived CNTF plays a significant role in promoting remyelination after demyelination.
