Dysregulation of LINGO1 expression in the SOD1(G93A) mutant mice during symptomatic stages of the disease and early postnatal oligodendrogenesis

The study of the SOD1(G93A) mutant mice model for amyotrophic lateral sclerosis (ALS) reveals a significant dysregulation of LINGO1 expression during symptomatic stages of the disease. LINGO1, a key inhibitor of oligodendrocyte differentiation and axonal regeneration, is notably elevated in both grey and white matter of the mutant spinal cord.

The protein expression is not only increased but also co-expressed with astroglial and neuronal markers. However, there is no alteration in the levels of LINGO1 transcripts or microRNAs known to regulate its expression, indicating alternative regulatory mechanisms at play. A significant downregulation of miR-138, a microRNA that promotes myelination, is observed in the mutant mice.

This disruption in LINGO1 and miR-138 expression may contribute to the deleterious processes that occur during disease progression in adulthood. Notably, white-matter pathology begins earlier than previously thought, with significant alterations in oligodendrogenesis evident as early as postnatal day 5. The study further reveals that increased miR-138 expression may promote oligodendrocyte progenitor cell maturation, potentially through compensatory mechanisms.

The findings suggest that disrupted expression of LINGO1 and/or miR-138 in brain during early oligodendrogenesis and at symptomatic disease stages could serve as potential biomarkers and therapeutic targets for promoting remyelination in the context of ALS.