Univ Coimbra, Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, and Coimbra Institute for Clinical and Biomedical Research (iCBR), Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Portugal.
Univ Coimbra, Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, and Coimbra Institute for Clinical and Biomedical Research (iCBR), Coimbra, Portugal.
Toxicol Lett. 2023 Nov 1;389:1-10. doi: 10.1016/j.toxlet.2023.10.008. Epub 2023 Oct 14.
Methylphenidate (MPH) has been used for decades to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Moreover, several studies have shown that it is subject to misuse, particularly among college students and adolescents, for cognitive enhancement or as a recreational drug. This phenomenon causes concern, and it is critical to clarify better how MPH impacts brain cells. In fact, data has suggested that MPH could result in neuroinflammation and neurodegeneration across several brain regions; however, little is known about the effect of MPH on glial cells. To address this, we used microglia N9 cell line and primary cultures of cortical astrocytes that were exposed to MPH (0.01 - 2 mM), as well as Wistar Kyoto rats (WKY) chronically administered with MPH (1.5 mg/kg/day). Several parameters were analyzed, and we concluded that MPH has no significant direct effect on microglial cells, apart from cell migration impairment. On the contrary, MPH promotes astrogliosis, oxidative/nitrosative stress, and increases proinflammatory cytokine TNF levels by astrocytes, which was concordant with the results obtained in the hippocampus of WKY rats. Overall, the present results suggest that brain cells respond differently to MPH, with a more prominent direct effect on astrocytes when compared to microglia.
哌醋甲酯（MPH）已被用于治疗注意力缺陷多动障碍（ADHD）和嗜睡症数十年。此外，多项研究表明，它存在被滥用的情况，尤其是在大学生和青少年中，被用作认知增强剂或娱乐性药物。这种现象引起了关注，因此更好地阐明 MPH 如何影响脑细胞至关重要。事实上，有数据表明，MPH 可能导致多个脑区的神经炎症和神经退行性变；然而，对于 MPH 对神经胶质细胞的影响知之甚少。为了解决这个问题，我们使用小胶质细胞 N9 细胞系和皮质星形胶质细胞原代培养物来暴露于 MPH（0.01-2mM），以及慢性给予 MPH（1.5mg/kg/天）的 Wistar Kyoto 大鼠（WKY）。分析了几个参数，我们得出结论，除了细胞迁移受损外，MPH 对小胶质细胞没有明显的直接作用。相反，MPH 通过星形胶质细胞促进神经胶质增生、氧化/硝化应激，并增加促炎细胞因子 TNF 的水平，这与 WKY 大鼠海马体的结果一致。总的来说，目前的结果表明，脑细胞对 MPH 的反应不同，与小胶质细胞相比，MPH 对星形胶质细胞的直接作用更为明显。
