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Regulation of Brain-Derived Neurotrophic Factor (BDNF) and Cerebral Dopamine Neurotrophic Factor (CDNF) by Anti-Parkinsonian Drug Therapy In Vivo

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Abstract

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 A2A 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.

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Acknowledgments

The authors would like to thank the following people for their support: Mart Saarma, University of Helsinki Biocenter, for expert consultations on CDNF; Mikko Airavaara, University of Helsinki Biocenter, for his support in establishing the microdissection protocol used in this study; Xue-fei Wu and Outi Nikkilä for their help with animal surgery; the staff of the animal facilities at the University of Helsinki Biocenter. This work was supported by a scholarship from Studienstiftung des deutschen Volkes (German National Academic Foundation).

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  1. Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014, Helsinki, Finland

    Tobias Gyárfás, Juha Knuuttila, Tomi Rantamäki & Eero Castrén

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Fetscherstr. 74, 01307, Dresden, Germany

    Tobias Gyárfás

  3. Institute of Biotechnology, Viikki Biocenter, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland

    Päivi Lindholm

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  1. Tobias Gyárfás
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Correspondence to Eero Castrén.

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Gyárfás, T., Knuuttila, J., Lindholm, P. et al. Regulation of Brain-Derived Neurotrophic Factor (BDNF) and Cerebral Dopamine Neurotrophic Factor (CDNF) by Anti-Parkinsonian Drug Therapy In Vivo. Cell Mol Neurobiol 30, 361–368 (2010). https://doi.org/10.1007/s10571-009-9458-3

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