Gene expression patterns for GDNF and its receptors in the human putamen affected by Parkinson's disease: a real-time PCR study.
Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta superfamily, is a potent trophic factor for dopaminergic neurons of the ventral midbrain, which are known to degenerate during Parkinson's disease (PD). The neuroprotective, neurorestorative, and stimulatory properties of GDNF has prompted numerous suggestions that this trophic factor may be a potential therapeutic tool to treat PD, and it has also been widely speculated that altered GDNF expression levels may be involved in the pathophysiology of the disease. In this study, we have investigated if mRNA expression levels for GDNF and/or its receptors are altered during PD in the human putamen, a target area for dopamine neurons of the substantia nigra compacta. Expression levels were analyzed with quantitative real-time reverse transcriptase polymerase reaction (RT qPCR) in post-mortem tissues from PD patients and aged matched controls. Primer pairs specific for GDNF (isoforms I and II), and its receptor molecules, GFRalpha1 and cRET were utilized. GDNF, cRET and GFRalpha1 mRNA expression was clearly detected in the putamen of control and Parkinson's disease patients. A modest but significant upregulation of GDNF mRNA levels (Isoform I) was observed in the putamen of Parkinson's disease patients with a marked loss of nigral neurons. No significant changes were observed for the expression of cRet and GFRa1. These data suggest that the extensive loss of dopaminergic neurons in the substantia nigra, and concomitant loss of striatal dopamine, may induce compensatory changes in the expression of target derived GDNF, but not its receptor system.
Bäckman
Cristina M
CM
Cellular Neurobiology Branch, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. cbackman@intra.nida.nih.gov
Shan
Lufei
L
Zhang
Ya Jun
YJ
Hoffer
Barry J
BJ
Leonard
Sherry
S
Troncoso
Juan C
JC
Vonsatel
Paul
P
Tomac
Andreas C
AC
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D002102:Cadaver; D002423:Cause of Death; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics*; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D011699:Putamen / Q000503:physiopathology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D020033:Protein Isoforms; D012313:RNA