The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, SE-751 24, Uppsala University, Sweden.
The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, SE-751 24, Uppsala University, Sweden.
J Steroid Biochem Mol Biol. 2021 Jun;210:105863. doi: 10.1016/j.jsbmb.2021.105863. Epub 2021 Mar 4.
The illicit use of anabolic androgenic steroids (AAS) among adolescents and young adults is a major concern due to the unknown and unpredictable impact of AAS on the developing brain and the consequences of this on mental health, cognitive function and behaviour. The present study aimed to investigate the effects of supra-physiological doses of four structurally different AAS (testosterone, nandrolone, stanozolol and trenbolone) on neurite development and cell viability using an in vitro model of immature primary rat cortical cell cultures. A high-throughput screening image-based approach, measuring the neurite length and number of neurons, was used for the analysis of neurite outgrowth. In addition, cell viability and expression of the Tubb3 gene (encoding the protein beta-III tubulin) were investigated. Testosterone, nandrolone, and trenbolone elicited adverse effects on neurite outgrowth as deduced from an observed reduced neurite length per neuron. Trenbolone was the only AAS that reduced the cell viability as indicated by a decreased number of neurons and declined mitochondrial function. Moreover, trenbolone downregulated the Tubb3 mRNA expression. The adverse impact on neurite development was neither inhibited nor supressed by the selective androgen receptor (AR) antagonist, flutamide, suggesting that the observed effects result from another mechanism or mechanisms of action that are operating apart from AR activation. The results demonstrate a possible AAS-induced detrimental effect on neuronal development and regenerative functions. An impact on these events, that are essential mechanisms for maintaining normal brain function, could possibly contribute to behavioural alterations seen in AAS users.
青少年和年轻成年人中非法使用合成代谢雄激素类固醇（AAS）是一个主要关注点，因为 AAS 对发育中的大脑的未知和不可预测的影响，以及对心理健康、认知功能和行为的影响。本研究旨在使用体外未成熟原代大鼠皮质细胞培养模型，研究四种结构不同的 AAS（睾酮、诺龙、司坦唑醇和群勃龙）的超生理剂量对神经突发育和细胞活力的影响。一种高通量筛选基于图像的方法，测量神经突长度和神经元数量，用于分析神经突生长。此外，还研究了细胞活力和 Tubb3 基因（编码蛋白质 beta-III 微管蛋白）的表达。睾酮、诺龙和群勃龙对神经突生长产生了不良影响，这可以从观察到的每个神经元的神经突长度减少中推断出来。群勃龙是唯一一种降低细胞活力的 AAS，表现为神经元数量减少和线粒体功能下降。此外，群勃龙下调了 Tubb3 mRNA 的表达。选择性雄激素受体（AR）拮抗剂氟他胺既不能抑制也不能抑制神经突发育的不良影响，这表明观察到的影响是由其他作用机制或作用机制引起的，这些机制与 AR 激活无关。研究结果表明，AAS 可能对神经元发育和再生功能产生有害影响。对这些对维持正常大脑功能至关重要的事件的影响，可能会导致 AAS 使用者出现行为改变。
