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000151649 0247_ $$2doi$$a10.1007/s00702-020-02189-9
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000151649 0247_ $$2ISSN$$a1435-1463
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000151649 0247_ $$2ISSN$$a0375-9245
000151649 0247_ $$2ISSN$$a0022-3026
000151649 037__ $$aDZNE-2020-01228
000151649 041__ $$aEnglish
000151649 082__ $$a610
000151649 1001_ $$aKeller, Sebastian$$b0
000151649 245__ $$a9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.
000151649 260__ $$aWien [u.a.]$$bSpringer$$c2020
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000151649 520__ $$aβ-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.
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000151649 650_2 $$2MeSH$$aAnimals
000151649 650_2 $$2MeSH$$aAstrocytes: drug effects
000151649 650_2 $$2MeSH$$aAstrocytes: enzymology
000151649 650_2 $$2MeSH$$aCarbolines: pharmacology
000151649 650_2 $$2MeSH$$aCells, Cultured
000151649 650_2 $$2MeSH$$aDopaminergic Neurons
000151649 650_2 $$2MeSH$$aMice, Inbred C57BL
000151649 650_2 $$2MeSH$$aMonoamine Oxidase
000151649 650_2 $$2MeSH$$aMonoamine Oxidase Inhibitors: pharmacology
000151649 650_2 $$2MeSH$$aNerve Growth Factors: metabolism
000151649 650_2 $$2MeSH$$aPhosphatidylinositol 3-Kinases
000151649 7001_ $$0P:(DE-HGF)0$$aPolanski, Witold Henryk$$b1$$eCorresponding author
000151649 7001_ $$aEnzensperger, Christoph$$b2
000151649 7001_ $$aReichmann, Heinz$$b3
000151649 7001_ $$0P:(DE-2719)2811732$$aHermann, Andreas$$b4$$udzne
000151649 7001_ $$aGille, Gabriele$$b5
000151649 773__ $$0PERI:(DE-600)1481655-6$$a10.1007/s00702-020-02189-9$$gVol. 127, no. 7, p. 999 - 1012$$n7$$p999 - 1012$$tJournal of neural transmission$$v127$$x1435-1463$$y2020
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