Neuronal Differentiation Affects Lingo-1 Variants Expression, Implications in Demyelinating Diseases

Lingo-1 is a Leucine-rich repeat and Ig domain-containing protein which is known as a powerful negative regulator of myelination and oligodendrocyte differentiation. Following the detection of different Lingo-1 variants and the main role of Lingo-1expression in various CNS diseases such as Multiple sclerosis, Alzheimer, Neuroblastoma and Glioblastoma we focused on neuronal differentiation and its effects on the mRNA expression of lingo-1 variants. Materials and Methods: Neuro2A cells with the convenientcharacteristic and ability to differentiate were used in this study. Differentiation was triggered by diverse concentration of Caffeine, Retinoic acid and BSA, as well as serum starvation. The neurite outgrowth was measured during various time points. Furthermore, the transcript levels of Lingo-1 and HPRT were evaluated by RT-PCR. Results: Results showed that Neuro2A cells as an undiffere ntiated neuronal cell line with neuronal and amoeboid stem cell morphology express only variant 1 of lingo-1. Fully differentiated neurons showed high levels of variant 2, as well as variant 1 mRNA. Also the FBS 0.01%, Retinoic acid 10uM and BSA 0.1% (24h and 48h) was shown to be the best condition for neuronal differentiation, although variant-2 would be expressed regardless of differentiation protocol. Conclusion: These findings may offer new pharmacological opportunities in order to target the most convenient variant of lingo-1, preserving the other lingo-1 functions in the body to lessen the unwanted side effects.