To leverage transcranial alternating current stimulation (tACS) at different frequencies to enhance remyelination in the cuprizone model of multiple sclerosis (MS).

Decades of research has yielded in the development of dozens of disease modifying therapies. Albeit effective in reducing relapse rates and MRI lesions, these therapies do not reverse existing lesions nor halt ongoing neurodegeneration. Previous preclinical studies have revealed that neuronal activity can influence remyelination and that different patterns of neuronal activity can be sensed by oligodendroglial cells. These techniques, however, are not translatable to people with MS due to their invasive nature. In that regard, we investigate the potential of non-invasive neuromodulation through tACS in the cuprizone model of MS.

8-week-old mice receive a cuprizone diet for six weeks ensuring near complete demyelination whereafter the mice are reverted to a normal diet during a week, allowing partial remyelination. During the withdrawal phase, the mice receive either tACS at 1,5 or 10 Hz or sham stimulation for five consecutive days. Readouts include cognitive tests such as the novel object location task and the y-maze as well as immunohistochemistry to detect oligodendrocyte precursor cells (OPCs), oligodendrocytes (OLs) and myelin. 

Our preliminary results indicate that 1 week of tACS at 10Hz leads to improved cognition as demonstrated by a significant improvement in discrimination index during the novel object location task. The improvements were not associated with enhanced remyelination nor with an increase in OPC differentiation in the corpus callosum and dentate gyrus.

Our findings suggest that tACS at 10 Hz for 1 week can improve spatial memory in a murine model of MS in a symptomatic way without influencing remyelination nor oligodendrogenesis. Future experiments with other frequencies and time windows will determine whether other stimulation paradigms are as effective in improving memory and whether oligodendrogenesis and remyelination can be accelerated.