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.

β-咔啉 (BC) 是吡啶并吲哚，可以在各种外源性和内源性来源中找到。最近的研究揭示了 9-甲基-BC (9-Me-BC) 的神经刺激、神经保护、神经再生和抗炎作用。此外，9-me-BC 增加了多巴胺能神经元的神经突生长，与这些神经元中的多巴胺摄取无关。在这项研究中，进一步探讨了星形胶质细胞在 9-me-BC 的神经刺激、神经再生和神经保护特性中的作用。

9-Me-BC 在多巴胺能中脑和皮质星形胶质细胞培养物中发挥抗增殖作用而无毒性。有机阳离子转运蛋白 (OCT) 而不是多巴胺转运蛋白似乎至少部分介导了 9-me-BC 对星形胶质细胞的影响。值得注意的是，9-me-BC 刺激了多巴胺能神经元（如 Artn、Bdnf、Egln1、Tgfb2 和 Ncam1）的几种重要神经营养因子的基因表达。众所周知，这些因素可刺激神经突生长，并对多巴胺能神经元表现出对抗各种毒素的神经保护和神经再生特性。此外，我们表明 9-me-BC 的作用是通过磷脂酰肌醇 3-激酶 (PI3K) 途径介导的。此外，9-me-BC 显示出对单胺氧化酶 (MAO) 活性的抑制特性，MAO-A 的 IC50 值为 1 µM，MAO-B 的 IC50 值为 15.5 µM。在最近的研究中，9-me-BC 对 MAO 的抑制可能有助于观察到 9-me-BC 处理后细胞培养物中多巴胺含量和抗凋亡特性的增加。因此，9-me-BC 对多巴胺能神经元具有过多的有益作用，值得将其作为一种新的多模式抗帕金森病药物进行探索。