EXPRESSION OF GDNF MESSENGER-RNA IN RAT AND HUMAN NERVOUS-TISSUE

A recently cloned neurotrophic factor, termed glial cell line-derived neurotrophic factor (GDNF), has been reported to exhibit selective neu rotrophic properties on ventral mesencephalon dopaminergic neurons, wh ich degenerate in patients with Parkinson's disease. In the present st udy, we used reverse transcriptase followed by polymerase chain reacti on (PCR) and in situ hybridization to study the expression of GDNF mes senger RNA (mRNA) in the adult rat and human central nervous system (C NS). GDNF transcripts were identified using PCR in all regions of the rat CNS analyzed including striatum, hippocampus, cortex, cerebellum, and spinal cord. Interestingly, the rat hippocampal formation containe d two transcripts, i.e., a larger form in addition to the amplified GD NF cDNA found in all other areas analyzed. GDNF PCR products also were observed in human striatum, hippocampus, cortex, and spinal cord, but not cerebellum, and both the striatum and hippocampal formation conta ined two GDNF transcripts. Finally, G;DNF transcripts were detected in a rat Schwann cell line previously shown to secrete a factor that exe rts a neurotrophic effect on dopaminergic neurons. In situ hybridizati on experiments using a cRNA probe hybridized to adult rat brain sectio ns demonstrated no positive GDNF mRNA signal. However, intense GDNF mR NA hybridization signal was found to be associated with dorsal root ga nglia in Postnatal Day 1 rats. These findings provide evidence that GD NF is detectable using PCR in a number of nervous system structures an d, in some areas, GDNF is expressed in more than one form. (C) 1994 Ac ademic Press, Inc.