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Regeneration and plasticity of descending propriospinal neurons after transplantation of Schwann cells overexpressing glial cell line-derived neurotrophic factor following thoracic spinal cord injury in adult rats

By Lingxiao Deng

Abstract

Indiana University-Purdue University Indianapolis (IUPUI)After spinal cord injury (SCI), poor axonal regeneration of the central nervous system, which mainly attributed to glial scar and low intrinsic regenerating capacity of severely injured neurons, causes limited functional recovery. Combinatory strategy has been applied to target multiple mechanisms. Schwann cells (SCs) have been explored as promising donors for transplantation to promote axonal regeneration. Among the central neurons, descending propriospinal neurons (DPSN) displayed the impressive regeneration response to SCs graft. Glial cell line-derived neurotrophic factor (GDNF), which receptor is widely expressed in nervous system, possesses the ability to promote neuronal survival, axonal regeneration/sprouting, remyelination, synaptic formation and modulate the glial response. We constructed a novel axonal permissive pathway in rat model of thoracic complete transection injury by grafting SCs over-expressing GDNF (SCs-GDNF) both inside and caudal to the lesion gap. Behavior evaluation and histological analyses have been applied to this study. Our results indicated that tremendous DPSN axons as well as brain stem axons regenerated across the lesion gap back to the caudal spinal cord. In addition to direct promotion on axonal regeneration, GDNF also significantly improved the astroglial environment around the lesion. These regenerations caused motor functional recovery. The dendritic plasticity of axotomized DPSN also contributed to the functional recovery. We applied a G-mutated rabies virus (G-Rabies) co-expressing green fluorescence protein (GFP) to reveal Golgi-like dendritic morphology of DPSNs and its response to axotomy injury and GDNF treatment. We also investigated the neurotransmitters phenotype of FluoroGold (FG) labeled DPSNs. Our results indicated that over 90 percent of FG-labeled DPSNs were glutamatergic neurons. DPSNs in sham animals had a predominantly dorsal-ventral distribution of dendrites. Transection injury resulted in alterations in the dendritic distribution, with dorsal-ventral retraction and lateral-medial extension of dendrites. Treatment with GDNF significantly increased the terminal dendritic length of DPSNs. The density of spine-like structures was increased after injury and treatment with GDNF enhanced this effect

Topics: Axonal regeneration, Descending propriospinal tract, Glia cell line derived neurotrophic factor, G-rabies virus, Schwann cell, Spinal cord injury, Central nervous system -- regeneration, Axons -- physiology, Central nervous system -- Physiology, Nervous system -- Regeneration, Spinal cord -- Wounds and injuries, Neuroglia
Year: 2015
OAI identifier: oai:scholarworks.iupui.edu:1805/7347
Provided by: IUPUIScholarWorks

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