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Journal of Neural Transmission
Article . 2020 . Peer-reviewed
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9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes

Authors: Keller, Sebastian; Polanski, Witold Henryk; Enzensperger, Christoph; Reichmann, Heinz; Hermann, Andreas; Gille, Gabriele;

9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes

Abstract

Abstractβ-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.

Country
Germany
Keywords

Dopaminergic Neurons [MeSH] ; Mice, Inbred C57BL [MeSH] ; Neurotrophic factors ; Phosphatidylinositol 3-Kinases [MeSH] ; Nerve Growth Factors/metabolism [MeSH] ; Monoamine Oxidase Inhibitors/pharmacology [MeSH] ; Astrocytes ; Animals [MeSH] ; Monoamine Oxidase [MeSH] ; Carbolines/pharmacology [MeSH] ; Astrocytes/drug effects [MeSH] ; Neurology and Preclinical Neurological Studies - Original Article ; Dopaminergic neurons ; Inhibition of monoamine oxidase A and B ; 9-Methyl-β-carboline ; Astrocytes/enzymology [MeSH] ; Cells, Cultured [MeSH], metabolism [Nerve Growth Factors], Monoamine Oxidase Inhibitors, Dopaminergic Neurons, drug effects [Astrocytes], pharmacology [Carbolines], Neurology and Preclinical Neurological Studies - Original Article, enzymology [Astrocytes], Mice, Inbred C57BL, Phosphatidylinositol 3-Kinases, Astrocytes, Animals, Nerve Growth Factors, Monoamine Oxidase, pharmacology [Monoamine Oxidase Inhibitors], Cells, Cultured, Carbolines, ddc: ddc:610

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Top 10%
Average
Average
Green
hybrid