Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases.Certain self-regeneration occurs in injured peripheral...Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases.Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion(DRG)neurons but does not occur in their central axonal branches.By performing rat sciatic nerve or dorsal root axotomy,we determined the expression of the dysbindin domain containing 2(DBNDD2)in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury,respectively,and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury.Furthermore,we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development.Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury.Bioinformatic analysis data showed that transcription factor estrogen receptor 1(ESR1)interacts with DBNDD2,exhibits a similar expression trend as DBNDD2 after axon injury,and may targets DBDNN2.These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.展开更多
基金supported by National Key R&D Program of China(Nos.2022YFC2409800 and 2022YFC2409802)Collegiate Natural Science Fund of Jiangsu Province(No.23KJA180006)Nantong University College Students’Innovative Entrepreneurial Training Plan Program(No.2023159).
文摘Effective axon regeneration is essential for the successful restoration of nerve functions in patients suffering from axon injury-associated neurological diseases.Certain self-regeneration occurs in injured peripheral axonal branches of dorsal root ganglion(DRG)neurons but does not occur in their central axonal branches.By performing rat sciatic nerve or dorsal root axotomy,we determined the expression of the dysbindin domain containing 2(DBNDD2)in the DRGs after the regenerative peripheral axon injury or the non-regenerative central axon injury,respectively,and found that DBNDD2 is down-regulated in the DRGs after peripheral axon injury but up-regulated after central axon injury.Furthermore,we found that DBNDD2 expression differs in neonatal and adult rat DRGs and is gradually increased during development.Functional analysis through DBNDD2 knockdown revealed that silencing DBNDD2 promotes the outgrowth of neurites in both neonatal and adult rat DRG neurons and stimulates robust axon regeneration in adult rats after sciatic nerve crush injury.Bioinformatic analysis data showed that transcription factor estrogen receptor 1(ESR1)interacts with DBNDD2,exhibits a similar expression trend as DBNDD2 after axon injury,and may targets DBDNN2.These studies indicate that reduced level of DBNDD2 after peripheral axon injury and low abundance of DBNDD2 in neonates contribute to axon regeneration and thus suggest the manipulation of DBNDD2 expression as a promising therapeutic approach for improving recovery after axon damage.
