THE EFFECT OF OLIGODENDROGLIAL-ADAM10 DEFICIENCY UPON CHEMICAL- OR MECHANICAL-INDUCED CENTRAL NERVOUS SYSTEM DEMYELINATION IN MICE

Demyelination of the central nervous system (CNS) involves the loss of myelin sheaths and/or oligodendrocyte death, leading to axonal degeneration and neurological deficits. It occurs in demyelinating disorders such as multiple sclerosis¹, as well as following mechanical insults like traumatic brain injury², where mechanical stretch can alter oligodendrocytes and promote demyelination³. Previous work from our group identified the α-secretase ADAM10 as a critical regulator of myelin sheath protection and repair after demyelination^4,5, suggesting its potential as a therapeutic target. ADAM10 is expressed by both neurons and glial cells, including oligodendrocytes, in the CNS⁶. We recently generated the KOOLA10 mouse model (ADAM10^f/fPLP-Cre), which allows conditional and inducible invalidation of ADAM10 specifically in oligodendrocytes. Our findings show that loss of oligodendroglial ADAM10 (OLA10) leads to behavioural deficits and myelin abnormalities in vivo, as well as impaired oligodendrocyte development and myelination in vitro⁷. The aim of this study is to investigate the role of OLA10 in CNS demyelination induced by chemical or mechanical injury. Chemical demyelination is examined in vivo using a lysolecithin-induced focal demyelination model in the adult mouse spinal cord⁸, recently established in our laboratory. Behavioural testing and immunohistochemical analyses of demyelination and inflammation on the lesion site are underway. Mechanical injury is modelled in vitro by subjecting primary oligodendrocyte cultures to equibiaxial mechanical stretch (30% strain for 30 min) using the Flexcell® Tension System. Oligodendrocyte morphology and maturation are being analysed. Together, these approaches will clarify the contribution of OLA10 to myelin protection and repair in distinct demyelinating contexts.