title: Amantadine and memantine induce the expression of the glial cell line-derived neurotrophic factor in C6 glioma cells.
abstract: Aminoadamantanes are commonly used in the treatment of Parkinson's and Alzheimer's diseases. While these drugs are shown to antagonise ionotropic glutamate receptors on neuronal cells, additional mechanisms could contribute to their neuroprotective properties. The aim of the present study was to investigate the effect of aminoadamantanes on the production of the glial cell line-derived neurotrophic factor (GDNF) in glial cells. For this purpose, we measured the modulation of GDNF release in C6 glioma cell cultures treated for 24 h with amantadine and memantine. Both drugs dose-dependently increased GDNF level in the culture medium with similar potency (submicromolar range) and efficacy (three to four-fold induction). RT-PCR studies revealed that both compounds also increased GDNF mRNA levels and their influence on the GDNF gene transcription was further evidenced using a rat GDNF promoter luciferase reporter assay. Together, these results demonstrate that the neuroprotective effect of amantadine and memantine could involve the regulation of GDNF production by glial cells.
authors.affiliation: Laboratoire de Pharmacologie Expérimentale (FARL), Université catholique de Louvain, Avenue Hippocrate 54.10, 1200 Bruxelles, Belgium.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Caumont
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Octave
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermans
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis*; D005910:Glioma / Q000378:metabolism*; D007118:Immunoassay; D008559:Memantine / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D020121:5' Untranslated Regions; D015259:Dopamine Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013778:Tetrazolium Salts; D013844:Thiazoles; D000547:Amantadine; C022616:thiazolyl blue; D008559:Memantine