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9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes
- Source :
- Journal of neural transmission 127(7), 999-1012 (2020). doi:10.1007/s00702-020-02189-9, Journal of Neural Transmission
- Publication Year :
- 2020
- Publisher :
- Springer, 2020.
-
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. Electronic supplementary material The online version of this article (10.1007/s00702-020-02189-9) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Monoamine Oxidase Inhibitors
metabolism [Nerve Growth Factors]
Neurite
Monoamine oxidase
drug effects [Astrocytes]
Neurology and Preclinical Neurological Studies - Original Article
Neuroprotection
Dopaminergic neurons
enzymology [Astrocytes]
03 medical and health sciences
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Neurotrophic factors
Dopamine
medicine
Animals
Nerve Growth Factors
ddc:610
Monoamine Oxidase
Biological Psychiatry
Cells, Cultured
pharmacology [Monoamine Oxidase Inhibitors]
Dopamine transporter
biology
Chemistry
9-Methyl-β-carboline
Dopaminergic Neurons
Dopaminergic
Correction
pharmacology [Carbolines]
Cell biology
Mice, Inbred C57BL
Psychiatry and Mental health
030104 developmental biology
medicine.anatomical_structure
Neurology
Astrocytes
Inhibition of monoamine oxidase A and B
biology.protein
Neurology (clinical)
030217 neurology & neurosurgery
Carbolines
medicine.drug
Astrocyte
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of neural transmission 127(7), 999-1012 (2020). doi:10.1007/s00702-020-02189-9, Journal of Neural Transmission
- Accession number :
- edsair.doi.dedup.....518a4cdfa60dee7fc88933668b725820