The Effect Of Nkx6.1 On The Progress Of Interneurons And Astrocytes After Spinal Cord Injury

Spinal cord injury is a common and destructive central nervous system disease,which often leads to dysfunction of motor,sensory and reflex functions below the lesion,as well as other pathological neurological disorders.It seriously degrades the welfare of patients,and aggravates economic burden to families and society.The incidence of spinal cord injury is increasing year by year.However,the pathophysiological mechanism of spinal cord injury is very complex and our comprehensive are still superficial.Therefore,the treatment of spinal cord injury is still not effective.The development of spinal cord is closely related to the proliferation,migration and differentiation of neural tube cells.In the early stages of development,neuroepithelial cells in the peripheral ventricular area first produce neurons;later,neuroepithelial cells turn to produce astrocytes and oligodendrocytes.On the one hand,interneurons is the main local loop connecting sensory neurons and motor neurons,which play an important role in the pathological changes after spinal cord injury and in the process of the responsive repair.On the other hand,the activated astrocytes are multiply proliferated and it causes the formation of glial scars after spinal cord injury.It is recognized that the formation of glial scars is one of the main reasons that hinder the regeneration and functional recovery of CNS axons in mammals after spinal cord injury.Nkx6.1 is a transcription factor expressed in the anterior and posterior neural progenitor cells in the ventral spinal cord.It has been proved that the normal expression of Nkx6.1 can promote the production of motoneurons and V2 interneurons in the development of embryonic spinal cord,but it can obviously inhibit the formation of V1 interneurons.Meanwhile,Nkx6.1 plays a key role in the production,migration and maturation of astrocytes after birth.Above all,we speculate that once the expression of Nkx6.1 is lost,it will affect the production of the interneurons in the injured spinal cord,and cause the formation of astrocytes to be blocked,and then affect the formation of glial scars.In order toverify our hypothesis,we firstly used Cre-lox P system and Rosa26 gene knock-in technology to specifically induce knock-out of Nkx6.1 and introduce lycopene marker gene in different neural precursor cells of the spinal cord of adult mice.Next we constructed a knock-out spinal cord injury model and performed the immunofluorescence staining.The staining results showed that many Nkx6.1+ cells migrated from ependyma after spinal cord injury,and at the same time,the ablation of Nkx6.1 one week later after spinal cord injury would hinder the formation of glial scar,and inhibit the production of V2 intermediate neurons by regulating the expression pattern of Pax6 in the central neural tube.According to these results,we infer that the deletion of Nkx6.1 may promote the production of V1 interneurons,which can balance the adverse effects on the functional recovery after injury caused by the production of V2 neurons blocked.Moreover,although there is a high probability of the formation of glial scars in the knockout mice of Nkx6.1 two weeks later after injury,compared with the control mice,the area of glial scars would be obviously reduced and the production would slow down after the deletion of Nkx6.1.Together,we think that the loss of Nkx6.1 expression is more beneficial than harmful to the functional recovery after injury.At present,the understanding of pathological changes and the mechanism of body repair after spinal cord injury is still unclear.Consider the transcription factors Nkx6.1 and Pax6 as intervention targets to spinal cord injury,which may be of great significance for the clinical treatment of adult spinal cord injury.