Neurotrophin-4/5 is a survival factor for embryonic midbrain dopaminergic neurons in enriched cultures.
Parkinson's disease is a prevalent neurological disease characterized by profound and incapacitating movement disorders. A common pathology in Parkinson's patients is degeneration of substantia nigra dopaminergic neurons that innervate the striatum and a corresponding decrease in striatal dopamine content. We now report that NT-4/5 can prevent the death of rat embryonic substantia nigra dopaminergic neurons in low density, enriched, primary cultures. Furthermore, these neurons express messenger RNA encoding the trkB receptor for NT-4/5 and transcripts for NT-4/5 are present in their environment. In addition, we demonstrate that NT-4/5 protects embryonic dopaminergic neurons from the toxic effects of the neurotoxin MPP+. Thus, NT-4/5 could be a physiological survival factor for midbrain dopaminergic neurons and may be useful as a therapeutic agent for Parkinson's disease.
Hynes
M A
MA
Department of Neuroscience, Genentech, Inc., South San Francisco, CA 94080.
Poulsen
K
K
Armanini
M
M
Berkemeier
L
L
Phillips
H
H
Rosenthal
A
A
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D004298:Dopamine / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010300:Parkinson Disease / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics; D013378:Substantia Nigra / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor; C071951:neurotrophin 5; D014446:Tyrosine 3-Monooxygenase; C073922:neurotrophin 4; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine