PMID- 11334998 OWN - NLM STAT- MEDLINE DCOM- 20010719 LR - 20190901 IS - 0165-3806 (Print) IS - 0165-3806 (Linking) VI - 127 IP - 2 DP - 2001 Apr 30 TI - Parallel induction of the formation of dopamine and its metabolites with induction of tyrosine hydroxylase expression in foetal rat and human cerebral cortical cells by brain-derived neurotrophic factor and glial-cell derived neurotrophic factor. PG - 111-22 AB - Brain-derived neurotrophic factor (BDNF; 50 ng/ml), dopamine (DA; 10 microM) and forskolin (Fsk; 10 microM) have previously been shown by this and other laboratories to induce the tyrosine hydroxylase (TH) enzyme in foetal human and rat cerebral cortex during specified sensitive developmental periods. In the present study, these findings were extended for human and rat cells by showing that the induced TH+ cells also produce dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). In addition to this, TH induction and DA plus DOPAC production was observed in foetal human and rat cerebral cortex by using glial-cell derived neurotrophic factor (GDNF) in place of BDNF. The degree of induction by GDNF (1-10 ng/ml) was similar to that produced by BDNF and did not increase further when the two neurotrophic factors were used together. The time-course of induction in human cultures was followed: GDNF was found to cause a more rapid induction process than BDNF during the first 2 weeks. However the degree of induction after 3 weeks was the same for both neurotrophic factors. Inhibitors of transcription (actinomycin D) or of translation (cycloheximide) eliminated all the increase in DA+DOPAC contents elicited by these compounds, indicating that de novo transcription and translation were required for increased expression of the TH and other related enzymes. The intracellular pathways by which these molecules exert this dopaminergic phenotype induction effect are discussed. This study indicates a new source of dopaminergic brain tissue for use as transplants to neurosurgically treat Parkinson's disease patients. FAU - Theofilopoulos, S AU - Theofilopoulos S AD - Department of Biochemistry, Imperial College of Science, Technology and Medicine, South Kensington, SW7 2AY, London, UK. FAU - Goggi, J AU - Goggi J FAU - Riaz, S S AU - Riaz SS FAU - Jauniaux, E AU - Jauniaux E FAU - Stern, G M AU - Stern GM FAU - Bradford, H F AU - Bradford HF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res Dev Brain Res JT - Brain research. Developmental brain research JID - 8908639 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (GDNF protein, human) RN - 0 (Gdnf protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Protein Synthesis Inhibitors) RN - 102-32-9 (3,4-Dihydroxyphenylacetic Acid) RN - 1CC1JFE158 (Dactinomycin) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - VTD58H1Z2X (Dopamine) SB - IM MH - 3,4-Dihydroxyphenylacetic Acid/analysis MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Dactinomycin/pharmacology MH - Dopamine/analysis/*biosynthesis/genetics MH - Female MH - Fetus/cytology/drug effects/enzymology MH - Gene Expression Regulation, Enzymologic/drug effects MH - Glial Cell Line-Derived Neurotrophic Factor MH - Glutamate Decarboxylase/analysis MH - Humans MH - Immunohistochemistry MH - Microtubule-Associated Proteins/analysis MH - *Nerve Growth Factors MH - Nerve Tissue Proteins/*pharmacology MH - Neurons/cytology/drug effects/*enzymology MH - Neuroprotective Agents/*pharmacology MH - Phenotype MH - Pregnancy MH - Protein Biosynthesis/drug effects MH - Protein Synthesis Inhibitors/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Transcription, Genetic/drug effects MH - Tyrosine 3-Monooxygenase/analysis/genetics/*metabolism EDAT- 2001/05/04 10:00 MHDA- 2001/07/20 10:01 CRDT- 2001/05/04 10:00 PHST- 2001/05/04 10:00 [pubmed] PHST- 2001/07/20 10:01 [medline] PHST- 2001/05/04 10:00 [entrez] AID - S0165380601001250 [pii] AID - 10.1016/s0165-3806(01)00125-0 [doi] PST - ppublish SO - Brain Res Dev Brain Res. 2001 Apr 30;127(2):111-22. doi: 10.1016/s0165-3806(01)00125-0.