Expression of neurotrophin-3 promotes axonal plasticity in the acute but not chronic injured spinal cord.
Previously, we reported that over-expression of neurotrophin-3 (NT-3) promoted sprouting of axons in the injured but not uninjured spinal cord, suggesting that processes associated with the injury such as Wallerian degeneration (WD) participated to induce the neuroplasticity. To determine whether NT-3-induced axonal sprouting depends upon processes associated with an acute injury, we uncoupled the injury and NT-3 over-expression in time. Rats were treated with a replicationdefective adenoviral vector carrying the NT-3 gene (Adv.NT-3) 2 weeks or 4 months after receiving a unilateral lesion of their corticospinal tract (CST). Adv.LacZ was used as a control vector. Morphometric analysis of axonal sprouting was performed to measure the number of CST axons that arise from the intact CST, traverse the midline, and grow into the gray matter of the lesioned side of the spinal cord where the NT-3 was over-expressed. The number of axons sprouting across the midline was greater in the rats treated with Adv.NT-3 than in the control groups when the Adv.NT-3 was delivered 2 weeks after injury. These axons persisted for at least 6 months after Adv.NT-3 delivery. In contrast, when Adv.NT-3 was delivered 4 months after lesion, there was no significant difference in the number of CST axons that crossed the midline compared to controls. Since the processes of WD would have resolved within 4 months after injury, these data demonstrate that products of WD are a potential source of the co-inducing signals that support neuroplasticity in the presence of NT-3.
Chen
Qin
Q
Center for Cell and Gene Therapy and Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA.
Zhou
Lijun
L
Shine
H David
HD
D000208:Acute Disease; D000256:Adenoviridae; D000818:Animals; D001369:Axons / Q000502:physiology*; D002908:Chronic Disease; D005260:Female; D005822:Genetic Vectors; D007150:Immunohistochemistry; D009473:Neuronal Plasticity / Q000502:physiology*; D020933:Neurotrophin 3 / Q000096:biosynthesis* / Q000235:genetics; D011712:Pyramidal Tracts / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*
D020933:Neurotrophin 3