Optogenetic stimulation promotes Schwann cell proliferation, differentiation, and myelination in vitro

Abstract

Schwann cells (SCs) constitute a crucial element of the peripheral nervous system, by structurally supporting the formation of myelin and conveying vital trophic factors to the nervous system. However, the functions of SCs in developmental and regenerative stages remain unclear. Here, we investigated how optogenetic stimulation (OS) of SCs regulates their development. In SC monoculture, OS substantially enhanced SC proliferation and the number of BrdU⁺-S100ß⁺-SCs over time. In addition, OS also markedly promoted the expression of both Krox20 and myelin basic protein (MBP) in SC culture medium containing dBcAMP/NRG1, which induced differentiation. We found that the effects of OS are dependent on the intracellular Ca²⁺ level. OS induces elevated intracellular Ca²⁺ levels through the T-type voltage-gated calcium channel (VGCC) and mobilization of Ca²⁺ from both inositol 1,4,5-trisphosphate (IP₃)-sensitive stores and caffeine/ryanodine-sensitive stores. Furthermore, we confirmed that OS significantly increased expression levels of both Krox20 and MBP in SC-motor neuron (MN) coculture, which was notably prevented by pharmacological intervention with Ca²⁺. Taken together, our results demonstrate that OS of SCs increases the intracellular Ca²⁺ level and can regulate proliferation, differentiation, and myelination, suggesting that OS of SCs may offer a new approach to the treatment of neurodegenerative disorders.