Open Access9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes
Author(s) -
Sebastian Keller,
Witold Polanski,
Christoph Enzensperger,
Heinz Reichmann,
Andreas Hermann,
Gabriele Gille
Publication year - 2020
Publication title -
journal of neural transmission
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.142
H-Index - 110
eISSN - 1435-1463
pISSN - 0300-9564
DOI - 10.1007/s00702-020-02189-9
Subject(s) - dopaminergic , neuroprotection , dopamine , neurotrophic factors , substantia nigra , neurite , dopamine transporter , pharmacology , glial cell line derived neurotrophic factor , astrocyte , chemistry , neuroscience , monoamine neurotransmitter , biology , biochemistry , central nervous system , receptor , serotonin , in vitro
β-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored. 9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication. Electronic supplementary material The online version of this article (10.1007/s00702-020-02189-9) contains supplementary material, which is available to authorized users.