Acid-Sensing Ion Channel 1 Deficiency Aggravates Cuprizone-Induced Demyelination, Axonal Damage and Microgliosis in Mice

White matter degeneration in multiple sclerosis (MS) is characterized by oligodendrocyte dysfunction and subsequent demyelination. To determine whether acid-sensing ion channel subtype 1 (ASIC1) contributes to oligodendrocyte-associated pathology under non-autoimmune conditions, the cuprizone model was used in wild-type (WT) and ASIC1-deficient (KO) mice. Axonal degeneration, microgliosis (IBA1), demyelination, and oligodendrocyte abundance were assessed in the medial Corpus Callosum. Cuprizone increased IBA1 positivity, axonal damage, and demyelination, and these effects appeared more pronounced in ASIC1 KO animals than in WT animals. ASIC1 deficiency was associated with increased APP+ axonal spheroid formation and reduced myelination scores. However, oligodendrocyte marker analyses did not indicate an additional reduction in oligodendrocyte survival after 3 weeks. Overall, these data support a role of ASIC1 in preserving myelin integrity, consistent with myelin maintenance rather than direct regulation of oligodendrocyte survival.