Abstract

A 20,000 dalton cationic polypeptide has been purified to homogeneity from extracts of neonatal rat skeletal muscle. The addition of the purified peptide to dissociated cultures of embryonic rat spinal cord neurons enhances the development of choline acetyltransferase and acetylcholine synthesis activities, but does not affect the overall metabolic activity of spinal cord cultures. This polypeptide represents the only skeletal muscle- derived neurotrophic factor purified to homogeneity, and besides NGF, it is the only other neurotrophic factor which affects cholinergic development of CNS-derived neurons. Treatment of chick embryos in ovo with the partially purified peptide during the normal cell death period rescues motor neurons which otherwise would have died. Thus, this neurotrophic peptide appears to be important for the survival and development of motor neurons. Our present efforts are directed at further characterization of the effects of this factor on the in vitro and in vivo development of motor neurons by direct application and through the development of specific antibodies to the purified factor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023058-06
Application #
3406088
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1985-12-01
Project End
1991-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Rabinovsky, E D; Ramchatesingh, J; McManaman, J L (1995) Regulation of tyrosine hydroxylase gene expression in IMR-32 neuroblastoma cells by basic fibroblast growth factor and ciliary neurotrophic factor. J Neurochem 64:2404-12
Rabinovsky, E D; Browder, D P; McManaman, J L (1994) Preparation and affinity purification of a novel, biologically active, CNTF fusion protein. J Neurosci Res 38:127-33
Rabinovsky, E D; Smith, G M; Browder, D P et al. (1992) Peripheral nerve injury down-regulates CNTF expression in adult rat sciatic nerves. J Neurosci Res 31:188-92
Houenou, L J; Haverkamp, L J; McManaman, J L et al. (1991) The regulation of motoneuron survival and differentiation by putative muscle-derived neurotrophic agents: neuromuscular activity and innervation. Development Suppl 2:149-55
Houenou, L J; McManaman, J L; Prevette, D et al. (1991) Regulation of putative muscle-derived neurotrophic factors by muscle activity and innervation: in vivo and in vitro studies. J Neurosci 11:2829-37
Oppenheim, R W; Haverkamp, L J; Prevette, D et al. (1988) Reduction of naturally occurring motoneuron death in vivo by a target-derived neurotrophic factor. Science 240:919-22
McManaman, J L; Haverkamp, L J; Appel, S H (1988) Developmental discord among markers for cholinergic differentiation: in vitro time courses for early expression and responses to skeletal muscle extract. Dev Biol 125:311-20
McManaman, J L; Crawford, F G; Stewart, S S et al. (1988) Purification of a skeletal muscle polypeptide which stimulates choline acetyltransferase activity in cultured spinal cord neurons. J Biol Chem 263:5890-7
Oppenheim, R W; Haverkamp, L J (1988) Neurotrophic interactions in the development of spinal cord motoneurons. Ciba Found Symp 138:152-71