Effects of Human Neural Stem Cells Overexpressing Neuroligin and Neurexin in a Spinal Cord Injury Model.
Jiwon JeongYunseo ChoiNarae KimHaneul LeeEun-Jung YoonDongsun ParkPublished in: International journal of molecular sciences (2024)
Recent studies have highlighted the therapeutic potential of stem cells for various diseases. However, unlike other tissues, brain tissue has a specific structure, consisting of synapses. These synapses not only transmit but also process and refine information. Therefore, synaptic regeneration plays a key role in therapy of neurodegenerative disorders. Neurexins (NRXNs) and neuroligins (NLGNs) are synaptic cell adhesion molecules that connect pre- and postsynaptic neurons at synapses, mediate trans-synaptic signaling, and shape neural network properties by specifying synaptic functions. In this study, we investigated the synaptic regeneration effect of human neural stem cells (NSCs) overexpressing NRXNs (F3.NRXN) and NLGNs (F3.NLGN) in a spinal cord injury model. Overexpression of NRXNs and NLGNs in the neural stem cells upregulated the expression of synaptophysin, PSD95, VAMP2, and synapsin, which are synaptic markers. The BMS scores indicated that the transplantation of F3.NRXN and F3.NLGN enhanced the recovery of locomotor function in adult rodents following spinal cord injury. Transplanted F3.NRXN and F3.NLGN differentiated into neurons and formed a synapse with the host cells in the spinal cord injury mouse model. In addition, F3.NRXN and F3.NLGN cells restored growth factors (GFs) and neurotrophic factors (NFs) and induced the proliferation of host cells. This study suggested that NSCs overexpressing NRXNs and NLGNs could be candidates for cell therapy in spinal cord injuries by facilitating synaptic regeneration.
Keyphrases
- spinal cord injury
- spinal cord
- neural stem cells
- stem cells
- cell therapy
- induced apoptosis
- prefrontal cortex
- neuropathic pain
- cell cycle arrest
- endothelial cells
- mouse model
- neural network
- signaling pathway
- gene expression
- poor prognosis
- cell proliferation
- endoplasmic reticulum stress
- cell adhesion
- pi k akt
- transcription factor
- healthcare
- oxidative stress
- wound healing
- drug induced
- high glucose
- stress induced
- young adults