Expression of GDNF receptor (RET and GDNFR-alpha) mRNAs in the spinal cordof patients with amyotrophic lateral sclerosis

The mRNA levels of RET and GDNFR-alpha were studied in the spinal cord of p atients with amyotrophic lateral sclerosis (ALS) by reverse transcription f ollowed by polymerase chain reaction (RT-PCR) and in situ hybridization (IS H). Semiquantitative RT-PCR analysis revealed that RET mRNA levels in the A LS spinal cord anterior horn were reduced to one fifth of controls in propo rtion to motor neuron loss, whereas GDNFR-alpha mRNA was unchanged. ISH ana lysis showed that RET mRNA was expressed in the anterior horn motor neurons of the spinal cord, but GDNFR-alpha mRNA was expressed widely in the spina l cord neurons and glial cells. The RET mRNA levels, measured using a CCD i mage analyzer, were substantially preserved in individual motor neurons of ALS, but varied among those neurons. Relatively high levels of RET mRNA wer e observed in a certain population of atrophic neurons. On the other hand, the GDNFR-alpha mRNA levels in the motor neurons were similar in ALS and co ntrols. In addition, the RET protein was also well expressed in individual motor neurons in ALS. These results indicate that GDNF receptor expression persists at mRNA and protein levels in the degenerating motor neurons in AL S, supporting the view that GDNF is a candidate for therapeutic approach to ALS. (C) 1999 Elsevier Science B.V. All rights reserved.