陆军军医大学学报 (Dec 2022)
Clemastine improves optic nerve myelin sheath regeneration and visual function in aged mice
Abstract
Objective To investigate the changes in myelin sheath of optic nerve in mice during the process of aging and explore the effect of clemastine, a pro-myelination drug, on visual function of aging mice. Methods The Cspg4-CreERt; mT/mG mice (4 and 13 months old) and wildtype C57/BL mice (4 and 13 months old) were employed in this study. The changes in number of oligodendrocytes (OLs) and newly-formed myelin were observed by immunofluorescence staining and quantitative immunoblotting. Their optical function was assessed with flash visual evoked potentials (fVEP). The reporter mice and wildtype mice at 13 months old were separately divided into control group and clemastine group. Immunostaining and fVEP test were used to observe the effects of clemastine on the newly-formed myelin and optical function. Results There was no significant difference in the density of NG2+ cells (oligodendrocyte precursor cells, OPCs) in the 13-month-old group in comparison with the 4-month-old group, but the count of CC1+ cells (mature OLs) was obviously decreased in the 13-month-old group (P < 0.01), and immunoblotting test also showed NG2+ protein level had no change between the groups. Immunofluorescence staining indicated that the area of mGFP+ NG2- (new myelin sheath) was declined greatly in the 13-month-old reporter mice (P < 0.05). fVEP test suggested that the latency of P2 wave was significantly prolonged in the 13-month-old group as compared with the 4-month-old group (P < 0.01). Clemastine treatment resulted in notably increased mGFP+ area (new myelin sheath) in the reporter mice (P < 0.05), and remarkably shorten the latency of P2 wave in 13-month-old mice (P < 0.01). Conclusion Inhibited myelinogenesis and decreased nerve conduction velocity in optic nerve are observed in aging mice. Clemastine treatment can greatly improve myelinogenesis and promote conduction velocity in optic nerve.
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