GLIA Porto 2019: Abstracts Oral Presentations, Posters, Indexes

Abstract

Research on demyelinating disorders has consistently demonstrated that cannabinoid agonists have the potential to relieve symptomatology and to control inflammatory-mediated neurodegeneration in Multiple sclerosis (MS) animal models and patients. Thus, the contribution of oligodendroglial cannabinoid receptors to the beneficial effects of cannabinoids in MS animal models has mostly focussed on their capacity to prevent cell survival of oligodendrocytes (OLs) and their progenitors (OPs) against excitotoxic injury. However, very few attention has been paid to the potential of targetting OPs by cannabis-based compounds to promote OL regeneration and functional recovery in demyelinating disorders. Here, we studied the effect of administering δ9- Tetrahydrocannabinol (δ9-THC) in OPs cell cycle dynamics and OL differentiation, both, during the critical periods of postnatal CNS myelination and under demyelination condition, by using the Cuprizone model. First, we studied the effect of administering δ9-THC at early postnatal ages in the process of OL development during the critical periods of subcortical white matter (SCWM) myelination. We found that acute δ9-THC administration induced OPs cell cycle exit and differentiation, accelerating the process of OL maturation, SCWM myelination, and motor function development at postnatal ages. Further, by using the Cuprizone animal model, we also found that acute δ9-THC administration following demyelination induced OPs cell cycle exit and differentiation, and accelerated the processes of OL regeneration and SCWM remyelination and motor function recovery. Moreover, THC effects on OL differentiation and regeneration involved the activation of CB1 and CB2 cannabinoid receptors, both, during postnatal development and during remyelination. Overall, our results show that acute δ9-THC administration induces OP cell cycle exit and differentiation, and accelerates OL development during CNS myelination, but also accelerates OL regeneration during CNS remyelination. This study addresses the therapeutic potential of targetting cannabis-based compounds to promote OL regeneration, myelin repair and functional recovery in demyelinating disorders.