Journal Article

DZNE-2020-01228

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.

Keller, S. ; Polanski, W. H. (Corresponding author) ; Enzensperger, C. ; Reichmann, H. ; Hermann, A.DZNE* ; Gille, G.

2020
Springer Wien [u.a.]

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Please use a persistent id in citations: doi:10.1007/s00702-020-02189-9

Abstract: 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.

Keyword(s): Animals (MeSH) ; Astrocytes: drug effects (MeSH) ; Astrocytes: enzymology (MeSH) ; Carbolines: pharmacology (MeSH) ; Cells, Cultured (MeSH) ; Dopaminergic Neurons (MeSH) ; Mice, Inbred C57BL (MeSH) ; Monoamine Oxidase (MeSH) ; Monoamine Oxidase Inhibitors: pharmacology (MeSH) ; Nerve Growth Factors: metabolism (MeSH) ; Phosphatidylinositol 3-Kinases (MeSH)

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Contributing Institute(s):

1. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Keller, S. ; Polanski, W. H. ; Enzensperger, C. ; Reichmann, H. ; Hermann, A.DZNE* ; Gille, G.
Correction to: 9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.
Journal of neural transmission 129(1), 125 (2022) [10.1007/s00702-021-02433-w]2022   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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