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 dopaminerg ic 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 de nsity, enriched, primary cultures. Furthermore, these neurons express messenger RNA encoding the trkB receptor for NT-4/5 and transcripts fo r NT-4/5 are present in their environment. In addition, we demonstrate that NT-4/5 protects embryonic dopaminergic neurons from the toxic ef fects of the neurotoxin MPP+. Thus, NT-4/5 could be a physiological su rvival factor for midbrain dopaminergic neurons and may be useful as a therapeutic agent for Parkinson's disease. (C) 1994 Wiley-Liss, Inc.