The role of GSK3β pathway in oligodendroglial progenitor cell (OPC) differentiation and remyelination after spinal cord injury (SCI)

Abstract

Background: Demyelination of is one of the major obstacle for axon regeneration and functional recovery after SCI. Previous research has shown that a pool of resident neural progenitor cells (NPCs) in spinal cord can be recruited to produce progeny after injury. Our preliminary study shows that lithium and noggin stimulate oligodendrocyte differentiation of adult spinal cord-derived NPC (ASCNPC) and lithium exerts its effect by inhibiting GSK3β pathway. Objective: To examine whether GSK3β inhibition leads to oligodendrocyte differentiation,and functional recovery after SCI. Method: Adult mice were subjected to contusive injury at 8th-10th thoracic level. Twenty-four hours after injury, spinal cord segments were harvested for neurosphere culture. Neurosphere cells were treated with GSK3β inhibitors ARA-014418 and lithium and cultured in differentiating medium. Four weeks after SCI, mice were treated with ARA-014418 and lithium for 2 weeks before the animals were sacrificed. Basso Mouse Scale (BMS) was performed weekly after injury to monitor locomotion function. Result: ARA-014418 and lithium promote both oligodendroglial and neuronal differentiation of ASCNPCs, . Injured mice treated with GSK3β inhibitors exhibit better performance in BMS. Conclusion: Both GSK3β inhibitors ARA-014418 and lithium are effective in promoting oligodendrocyte/neuron differentiation and functional recovery after SCI. It indicates that GSK3β is a key player in impeding SCI repair.