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

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 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.

The effects of motor rehabilitation training on clinical symptoms and serum BDNF levels in Parkinson’s disease subjects

“…BDNF is a potent trophic factor for these neurons (Hyman et al 1991) and is involved in synaptic plasticity (Gómez-Palacio-Schjetnan and Escobar 2013). Its potential involvement in PD is supported by the fact that PD patients are characterized by low levels of circulating BDNF (Scalzo et al 2010) and antiparkinsonian drugs may increase these levels in PD mouse models (Gyárfás et al 2010). Moreover, similar treatments, such as physical exercise as well as environmental enrichment, may upregulate BDNF in the brain (Gelfo et al 2011;Kleim et al 2003) and confer resistance to neurodegeneration in PD rodent models (Lau et al 2011).…”

The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice

“…Third, up-regulation of BDNF or BDNF-mediated signaling was involved in neuroprotection process of dopaminergic neurons against inflammatory, MPTP, and 6-OHDA-induced degeneration by mediating retinoic acid receptor stimulation, cystamine administration and acupuncture [16,23,33]. The rasagiline and selegiline, two anti-PD monoamine oxidase-B inhibitors, possessed neuroprotective activities and promoted regeneration of nigral dopaminergic neurons in MPTP model by inducing production of BDNF, activating of Trk receptor pathway and increasing of downstream effector phosphatidylinositol 3 kinase protein [18,25]. Fourth, the aging-related changes in gene expression of nigra and striatum were observed in BDNF heterozygous mice [39] and inhibition of BDNF expression by antisense oligonucleotide infusion also confirmed a loss of nigral dopaminergic neurons [34].…”

“…These positive cells are representatively shown with arrowheads. SNc substantia nigra pars compacta, SNr substantia nigra pars reticularis evidence on its functional relationship with cerebral dopamine neurotrophic factor, pigment epithelium derived factor and TGF-beta that were also involved in dopaminergic neuronal development, maintenance and neuroprotection [14,18,35]. Indeed, protective effects of neurotrophic factor-secreting cells were reported in a rat 6-OHDA model of PD [36].…”

Effect of Tandospirone on Mismatch Negativity and Cognitive Performance in Schizophrenia

“…This assumption is based on observations that blockade of NMDA receptors reduces MMN 9,19 and that 8-OH-DPAT, a 5-HT 1A agonist, modulates cortical activity through 5-HT 1A receptors located on GABAergic interneurons and those on pyramidal neurons. 20 Further study is needed to confirm the potential benefit of agents acting on 5-HT 1A receptors for improving MMN and other components of ERPs in people with schizophrenia.…”