Regulation of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) by anti-parkinsonian drug therapy in vivo.
Available treatment for Parkinson's disease (PD) is mainly symptomatic instead of halting or reversing degenerative processes affecting the disease. Research on the molecular pathogenesis of PD has suggested reduced trophic support as a possible cause or mediator of neurodegeneration. In animal models of the disease, neurotrophic factors prevent neurodegeneration and induce behavioral recovery. Some anti-Parkinsonian drugs show neuroprotective activity, but it is not known whether the drug-induced neuroprotection is mediated by neurotrophic factors. In this study, we have investigated the influence of two neuroprotective anti-Parkinsonian drugs, the monoamine oxidase B inhibitor selegiline and the adenosine A(2A) antagonist SCH 58261, on the levels of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) in the mouse brain. Protein levels of BDNF and CDNF were quantified by western blot after 2 weeks of treatment with either of the drugs or placebo. CDNF levels were not significantly influenced by selegiline or SCH 58261 in any brain area studied. Selegiline treatment significantly increased BDNF levels in the anterior cingulate cortex (1.55 +/- 0.22, P < 0.05, Student's t-test). In the striatum, selegiline increased BDNF content by 32%, but this change did not reach statistical significance (1.32 +/- 0.15, P < 0.13, Student's t-test). Our data suggest that neurotrophic factors, particularly BDNF may play a role in the neuroprotective effects of selegiline, but do not support the hypothesis that anti-Parkinsonian drugs would work by increasing the levels of CDNF in brain.
Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland.
Tobias
T
Gyárfás
Juha
J
Knuuttila
Päivi
P
Lindholm
Tomi
T
Rantamäki
Eero
E
Castrén
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy*; D011743:Pyrimidines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D019208:Brain-Derived Neurotrophic Factor; D008996:Monoamine Oxidase Inhibitors; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C522218:cdnf protein, mouse; D012642:Selegiline