10 Hz tACS Promotes Myelin Repair and Improves Spatial Memory Following Cuprizone-induced Demyelination
Thomas Scheinok1, Jeroen Van Schependom2, Dimitri De Bundel2
1Neurology, Vrije Universiteit Brussel/ UZ Brussel, 2Vrije Universiteit Brussel
Objective:
To investigate whether transcranial alternating current stimulation (tACS) at 10 Hz can promote remyelination and improve cognitive function following cuprizone-induced demyelination.
Background:
Multiple sclerosis (MS) is characterised by demyelinating plaques and the inability to remyelinate. This failure not only leads to symptoms due to acute demyelination but also worsens disability as a consequence of axonal degeneration. To this date, research has largely focused on preventing demyelination through immune-modulating therapies. While successful in reducing relapse rates, disease progression and cognitive decline continue. This has led to a paradigm shift towards therapies aimed at promoting remyelination. One promising approach involves modulating neuronal activity, as several in vitro and in vivo studies have shown a link between electrically active axons and myelination. However, these protocol are not easily translatable to people with MS. To address this limitation, our study explores the potential of tACS to enhance remyelination.
Design/Methods:
Eight-week-old mice are subjected to a cuprizone diet for six week, inducing near-complete demyelination. After this phase, they are switched back to a normal diet for one week allowing partial remyelination. During this remyelination phase, mice undergo tACS at 10 Hz for five consecutive days. After the stimulation, cognitive performances are assessed using the Y-maze and novel object location task. Histological analyses include immunohistochemistry to detect proliferation and differentiation of oligodendrocyte precursor cells (OPCs) into oligodendrocytes (OLs) and transmission electron microscopy to asses myelin structure.
Results:
Our results indicate that one week of tACS at 10 Hz improves spatial memory, demonstrated by an improved discrimination index in the novel object location task. This cognitive improvement was accompanied by faster differentiation of newly born OPCs into mature OLs and thicker myelin as evidenced by a lower g-ratio.
Conclusions:
One week of tACS 10 Hz can enhance spatial memory and accelerate oligodendrogenesis, leading to improved remyelination.
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