Abstract

BackgroundThe regenerative ability of severed axons in the central nervous system is limited in mammals. However, after central nervous system injury, neural function is partially recovered by the formation of a compensatory neural circuit. In a mouse pyramidotomy model, axonal sprouting of the intact side of the corticospinal tract is observed in the spinal cord, and the axons make new synapses with the denervated side of propriospinal neurons. Moreover, this sprouting ability is enhanced in neonatal mice compared to that in adult mice. Myelin-associated molecules in the spinal cord or intrinsic factors in corticospinal neurons have been investigated in previous studies, but the factors that determine elevated sprouting ability in neonatal mice are not fully understood. Further, in the early phase after pyramidotomy, glial responses are observed in the spinal cord. To elucidate the basal difference in the spinal cord, we compared gene expression profiles of entire C4–7 cervical cord tissues between neonatal (injured at postnatal day 7) and adult (injured at 8 weeks of age) mice by RNA-sequencing. We also tried to identify discordant gene expression changes that might inhibit axonal sprouting in adult mice at the early phase (3 days) after pyramidotomy.ResultsA comparison of neonatal and adult sham groups revealed remarkable basal differences in the spinal cord, such as active neural circuit formation, cell proliferation, the development of myelination, and an immature immune system in neonatal mice compared to that observed in adult mice. Some inflammation-related genes were selectively expressed in adult mice after pyramidotomy, implying the possibility that these genes might be related to the low sprouting ability in adult mice.ConclusionsThis study provides useful information regarding the basal difference between neonatal and adult spinal cords and the possible differential response after pyramidotomy, both of which are necessary to understand why sprouting ability is increased in neonatal mice compared to that in adult mice.

Highlights

  • The regenerative ability of severed axons in the central nervous system is limited in mammals

  • First, to compare the sprouting ability between neonatal and adult mice after corticospinal tract (CST) injury, we injured the left pyramid of the medulla oblongata of postnatal day 7 (P7) neonatal mice or 8-week-old (8 W) adult mice

  • 2 weeks after injury, we injected anterograde tracer biotinylated or tetramethylrhodamine conjugated dextran amine into the intact side of the forelimb area of the motor cortex to label the axon of Corticospinal neuron (CSN)

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Summary

Introduction

The regenerative ability of severed axons in the central nervous system is limited in mammals. In a mouse pyramidotomy model, axonal sprouting of the intact side of the corticospinal tract is observed in the spinal cord, and the axons make new synapses with the denervated side of propriospinal neurons. This sprouting ability is enhanced in neonatal mice compared to that in adult mice. The axonal branch of the intact side of the CST grows into the denervated side of the cervical cord and forms synapses with the propriospinal neuron approximately 4 weeks after brain injury in mice [4]

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