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

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.

β-Carbolines in Experiments on Laboratory Animals

“…These results may be considered an effect of the positive impact of a diet enriched with β-carbolines on aged individuals. Some literature data reported that 9-me-BC lowered the content of α-synuclein in the primary dopaminergic cell cultures [ 27 ], as well as stimulated the gene expression of several important neurotrophic factors like Artn, Bdnf, Egln1, Tgfb2, and Ncam1, which are known to stimulate neurite outgrowth and exhibit neuroprotective and neuroregenerative properties to dopaminergic neurons [ 53 ].…”

Total flavonoids of hawthorn leaves protect spinal motor neurons via promotion of autophagy after spinal cord injury

“…Although past research has determined that hyperactivated astrocytes form glial scars after SCI, preventing nerve fibers from repairing and inhibiting neuronal axon growth ( Okada et al, 2018 ). With the deepening of related research, many researchers have found that astrocytes can secrete neurotrophic factors and other neuronal support substances to endorse the repair of damaged neurons ( Keller et al, 2020 ; Linnerbauer and Rothhammer, 2020 ). Furthermore, the degree of neuronal repair and its functional recovery is largely dependent on the growth of nascent axons.…”