Abstract

The long term goal of the proposed research is to identify, and to characterize biochemically and biologically, putative CNS-derived neurotrophic agents that influence the survival and development of spinal motoneurons (MNS) in the chick embryo. By capitalizing on our prior work indicating that a protein(s) derived from chicken CNS can promote the in vitro and in vivo survival on MNS, we will attempt to isolate and identify this agent(s) using standard methods of protein chemistry. We will also examine the in vitro and in vivo effects of members of the NGF or neurotrophin family on MN survival (e.g., NGF, BDNF, NT-3, and possibly NT-4 and NT-5). Finally, we will examine the in vivo expression of mRNAs for suspected trophic agents and their receptors in the avian CNS using in situ hybridization methodology. These include: NGF, FGF, CNTF, S100, BDNF and NT-3. The major significance of these studies is that they represent the first attempt to demonstrate that putative CNS-derived neurotrophic agents can act in vitro and in vivo to promote the survival of a population of neurons (MNS) that are at risk in human motor neuron diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS031380-01
Application #
3418312
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1993-03-01
Project End
1997-02-28
Budget Start
1993-03-01
Budget End
1994-02-28
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106

  Publications

Keiger, C Jane H; Prevette, David; Conroy, William G et al. (2003) Developmental expression of nicotinic receptors in the chick and human spinal cord. J Comp Neurol 455:86-99
Li, L; Oppenheim, R W; Milligan, C E (2001) Characterization of the execution pathway of developing motoneurons deprived of trophic support. J Neurobiol 46:249-64
Oppenheim, R W; Prevette, D; D'Costa, A et al. (2000) Reduction of neuromuscular activity is required for the rescue of motoneurons from naturally occurring cell death by nicotinic-blocking agents. J Neurosci 20:6117-24
Oppenheim, R W; Houenou, L J; Parsadanian, A S et al. (2000) Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: regulation of programmed cell death among motoneuron subtypes. J Neurosci 20:5001-11
Steljes, T P; Kinoshita, Y; Wheeler, E F et al. (1999) Neurotrophic factor regulation of developing avian oculomotor neurons: differential effects of BDNF and GDNF. J Neurobiol 41:295-315
Oppenheim, R W; Homma, S; Marti, E et al. (1999) Modulation of early but not later stages of programmed cell death in embryonic avian spinal cord by sonic hedgehog. Mol Cell Neurosci 13:348-61
Li, L; Houenou, L J; Wu, W et al. (1998) Characterization of spinal motoneuron degeneration following different types of peripheral nerve injury in neonatal and adult mice. J Comp Neurol 396:158-68
D'Costa, A P; Prevette, D M; Houenou, L J et al. (1998) Mechanisms of insulin-like growth factor regulation of programmed cell death of developing avian motoneurons. J Neurobiol 36:379-94
Grieshammer, U; Lewandoski, M; Prevette, D et al. (1998) Muscle-specific cell ablation conditional upon Cre-mediated DNA recombination in transgenic mice leads to massive spinal and cranial motoneuron loss. Dev Biol 197:234-47
Caldero, J; Prevette, D; Mei, X et al. (1998) Peripheral target regulation of the development and survival of spinal sensory and motor neurons in the chick embryo. J Neurosci 18:356-70

Showing the most recent 10 out of 24 publications