TY  - JOUR
AU  - Keller, Sebastian
AU  - Polanski, Witold Henryk
AU  - Enzensperger, Christoph
AU  - Reichmann, Heinz
AU  - Hermann, Andreas
AU  - Gille, Gabriele
TI  - 9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.
JO  - Journal of neural transmission
VL  - 127
IS  - 7
SN  - 1435-1463
CY  - Wien [u.a.]
PB  - Springer
M1  - DZNE-2020-01228
SP  - 999 - 1012
PY  - 2020
AB  - 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.
KW  - Animals
KW  - Astrocytes: drug effects
KW  - Astrocytes: enzymology
KW  - Carbolines: pharmacology
KW  - Cells, Cultured
KW  - Dopaminergic Neurons
KW  - Mice, Inbred C57BL
KW  - Monoamine Oxidase
KW  - Monoamine Oxidase Inhibitors: pharmacology
KW  - Nerve Growth Factors: metabolism
KW  - Phosphatidylinositol 3-Kinases
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC8592951
C6  - pmid:32285253
DO  - DOI:10.1007/s00702-020-02189-9
UR  - https://pub.dzne.de/record/151649
ER  -