Non-invasive visual theta entrainment modulates myelin-related and functional outcomes in an LPC-induced demyelination model

Demyelination is a hallmark of various neurodegenerative diseases, including multiple sclerosis (MS), leading to impaired neural transmission and motor deficits. The Lysophosphatidylcholine (LPC)-induced demyelination model is widely used because it reflects many aspects of demyelinating pathology. This study examined how non-invasive 4 Hz visual theta oscillation entrainment affects LPC-induced demyelination in the optic chiasm of male C57BL/6J mice. Mice received daily one-hour sessions of 4 Hz stimulation for two weeks post-LPC injection. The analysis of the VEPs showed that the latency of P1 waves was shorter in the theta stimulation group and significantly different from the LPC group on days 7 and 14. IBA1 immunostaining showed reduced IBA1 immunoreactivity at early post-lesion time points, while qPCR analysis showed lower Aif-1 1 and Gfap transcript levels in the theta-stimulated group. Luxol Fast Blue (LFB) and FluoroMyelin staining suggested greater preservation of myelin staining in the theta group at day 14. In parallel, molecular analyses revealed increased expression of oligodendrocyte-lineage markers, including Pdfgra at days 3 and 7 and Olig2 and Plp1 at day 14. Taken together, these findings suggest that theta oscillation entrainment modulates the molecular, cellular and electrophysiological responses that follow demyelinating injury, and that it may also influence the processes associated with myelin repair. Further studies are needed to clarify the mechanisms underlying these effects and to assess the therapeutic relevance of this non-invasive approach for demyelinating disorders.