Glial-cell-line-derived neurotrophic factor enhances biosynthesis of substance P in striatal neurons in vitro.
Glial-cell-line-derived neurotrophic factor (GDNF) is a novel trophic factor with potent trophic effects on several neuron populations in the central and peripheral nervous system. In the present study, we have investigated and compared the potential of dopamine and metamphetamine with that of the two striatal neurotrophic factors, viz., GDNF and neurotrophin-(NT)-4/5, to regulate substance P and its preprotachykinin-A mRNA in organotypic striatal slices from postnatal (day 10) rats. Incubation for 2 weeks with 10 ng/ml GDNF significantly increased substance-P-like immunoreactivity determined by radioimmunoassay. Similarly, the corresponding preprotachykinin-A mRNA increased after 1 and 2 weeks of incubation, as analyzed by in situ hybridization. NT-4/5 exhibited similar effects. The dopamine-releasing agent metamphetamine stimulated substance-P-containing neurons in 1-week-old striatal slices, whereas dopamine stimulated substance-P-like immunoreactivity in 1- and 2-week old striatal cultures. The effects of dopamine and GDNF were not additive. We conclude that substance-P-containing medium-sized spiny neurons in the striatum are under both dopaminergic and growth factor control by GDNF and NT-4/5, which are both synthesized in the striatum. This adds a previously unknown role to those that have been established for GDNF in the nigrostriatal system.
Humpel
C
C
Neurochemical Unit, Department of Psychiatry, University Hospital Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. christian.humpel@uibk.ac.at
Marksteiner
J
J
Saria
A
A
D000818:Animals; D015415:Biomarkers; D018491:Dopamine Agonists / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D017072:Neostriatum / Q000166:cytology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009434:Neural Pathways; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D013373:Substance P / Q000096:biosynthesis* / Q000235:genetics; D013378:Substantia Nigra / Q000166:cytology; D015320:Tachykinins / Q000235:genetics; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D018491:Dopamine Agonists; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D014446:Tyrosine 3-Monooxygenase; C073922:neurotrophin 4