Pharmacological treatment promoting remyelination enhances motor function after internal capsule demyelination in mice.

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system characterized by remyelination failure, axonal degeneration, and progressive worsening of motor functions. Animal models of demyelination are frequently used to develop and evaluate therapies for MS. We recently reported that focal internal capsule (IC) demyelination in mice with lysophosphatidylcholine injection induced acute motor deficits followed by recovery through remyelination. However, it remains unknown whether the IC demyelination mouse model can be used to evaluate changes in motor functions caused by pharmacological treatments that promote remyelination using behavioral testing and histological analysis. In this study, we examined the effect of clemastine, an anti-muscarinic drug that promotes remyelination, in the mouse IC demyelination model. Clemastine administration improved motor function and changed forepaw preference in the IC demyelinated mice. Moreover, clemastine-treated mice showed increased mature oligodendrocyte density, reduced axonal injury, an increased number of myelinated axons and thicker myelin in the IC lesions compared with control (PBS-treated) mice. These results suggest that the lysophosphatidylcholine-induced IC demyelination model is useful for evaluating changes in motor functions following pharmacological treatments that promote remyelination.

• Authors: Reiji Yamazaki, Yasuyuki Osanai, Tom Kouki, Jeffrey K Huang, Nobuhiko Ohno
• Journal: Neurochemistry international (Neurochem Int) Vol. 164 Pg. 105505 (03 2023) ISSN: 1872-9754 [Electronic] England
• PMID: 36754122 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Lysophosphatidylcholines
• Clemastine
• Cuprizone

Topics

• Mice
• Animals
• Remyelination
• Demyelinating Diseases (chemically induced)
• Lysophosphatidylcholines
• Clemastine (adverse effects)
• Internal Capsule (pathology)
• Myelin Sheath (pathology)
• Multiple Sclerosis (pathology)
• Oligodendroglia
• Mice, Inbred C57BL
• Disease Models, Animal
• Cuprizone (pharmacology)