It is proposed to investigate regeneration of goldfish optic axons with the following specific aims: I. To examine the role of phosphorylation of axonally transported proteins by investigating (a) the nature of the changes in protein phosphorylation that occur during regeneration; (b) the protein kinases responsible for these changes; (c) how agents that modulate protein phosphorylation affect regeneration, and (d) how alterations in the time course of regeneration affect the sequence of changes in phosphorylation. II. To determine how some axonally transported constituents involved in synaptic function change during regeneration, particularly with respect to whether or not the regenerating axons have formed retinotopically correct connections. The constituents to be investigated would be synapsin I, nicotinic acetylcholine receptors (defined by alpha-bungarotoxin binding), and acetylcholinesterase. III. To investigate the role of phosphorylation of proteins in the interaction between axons and glial cells, based on our observation that when the axons have degenerated the glial cells do not phosphorylate the same array of proteins as when the axons are intact. Major techniques in this study would be the analysis of phosphorylated proteins by 2-dimensional gel electrophoresis and HPLC, applied to studies of regenerating axons and studies of glial cells in vivo and in vitro. The overall objective is to analyses the properties of a successfully regenerating neuron, in order to further our understanding of the process of axonal regeneration and the mechanisms involved in its regulation. The ultimate application of this knowledge would be in developing techniques for promoting regeneration following damage to the central nervous system produced by conditions such as spinal cord injury, stroke or cerebral palsy, and would also have relevance for studies of Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS014967-09
Application #
3395869
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1979-07-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1992-03-31
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
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Thormodsson, F R; Antonian, E; Grafstein, B (1992) Extracellular proteins of goldfish optic tectum labeled by intraocular injection of 3H-proline. Exp Neurol 117:260-8
Larrivee, D (1991) Relationship between tubulin delivery and synapse formation during goldfish optic nerve regeneration. Ann N Y Acad Sci 627:368-71
Perry, G W; Burmeister, D W; Grafstein, B (1990) Effect of target removal on goldfish optic nerve regeneration: analysis of fast axonally transported proteins. J Neurosci 10:3439-48
Larrivee, D (1990) Protein phosphorylation: localization in regenerating optic axons. Neurochem Res 15:875-80
Reich, J B; Burmeister, D W; Schmidt, J T et al. (1990) Effect of conditioning lesions on regeneration of goldfish optic axons: time course of the cell body reaction to axotomy. Brain Res 515:256-60
Larrivee, D C; Grafstein, B (1989) Relationship between phosphorylation and synthesis of goldfish optic nerve proteins during regeneration. J Neurosci 9:574-81
Larrivee, D C; Grafstein, B (1987) In vivo phosphorylation of axonal proteins in goldfish optic nerve during regeneration. J Neurochem 48:279-83
Larrivee, D C; Grafstein, B (1987) Phosphorylation of proteins in normal and regenerating goldfish optic nerve. J Neurochem 49:1747-57
Burmeister, D W; Dunn-Meynell, A A (1987) Recovery of regenerating goldfish retinal ganglion cells is slowed in the absence of the topographically correct synaptic target. Brain Res 423:56-62

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