Spinal cord regeneration remains among the most elusive problems in neuroscience. While much is known of the pathology, the underlying cellular mechanisms which promote regeneration are poorly understood. With advancements in technology, transplantation methods provide one way to investigate this basic problem, and also a potential way to reconstruct the CNS. This proposal focuses on transplants of embryonic catecholamine (CA) nerve cells in the adult spinal cord (rat). These cells provide a highly measurable experimental system for morphological, biochemical and functional assessments.
Aim 1 experiments are designed to develop and define a behavioral model for catecholamine (CA) denervation of the spinal cord.
The Aim 2 experiments are designed to determine if transplants of embryonic neurons (CA and spinal cord) restore the behavioral deficits defined Aim 1. Selective elimination of the descending CA fibers in the thoracolumbar level of the cord will be done with neurotoxin 6- OHDA. Four distinctly different behavioral measures will be assessed following the selective denervation - locomotor activity, coordination and balance, strength of hind-limb response, and hindlimb extension. These behavioral measures will be correlated with biochemical (HPLC) and morphological (histofluorescence) measures of CA levels in the brainstem and all regions of the spinal cord. This research will provide information on the role of the descending CA system in motor behaviors, and determine whether transplants can restore motor deficits in the adult spinal cord.
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