The mRNA levels of RET and GDNFR-α were studied in the spinal cord of patients with amyotrophic lateral sclerosis (ALS) by reverse transcription followed by polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). Semiquantitative RT-PCR analysis revealed that RET mRNA levels in the ALS spinal cord anterior horn were reduced to one fifth of controls in proportion to motor neuron loss, whereas GDNFR-α mRNA was unchanged. ISH analysis showed that RET mRNA was expressed in the anterior horn motor neurons of the spinal cord, but GDNFR-α mRNA was expressed widely in the spinal cord neurons and glial cells. The RET mRNA levels, measured using a CCD image analyzer, were substantially preserved in individual motor neurons of ALS, but varied among those neurons. Relatively high levels of RET mRNA were observed in a certain population of atrophic neurons. On the other hand, the GDNFR-α mRNA levels in the motor neurons were similar in ALS and controls. 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 ALS, supporting the view that GDNF is a candidate for therapeutic approach to ALS.
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