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Structurally different anabolic androgenic steroids reduce neurite outgrowth and neuronal viability in primary rat cortical cell cultures
- Publication Year :
- 2021
- Publisher :
- Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Anabolic androgenic steroids
Primary cortical cell culture
Biochemistry
Pharmaceutical Sciences
Anabolic Agents
0302 clinical medicine
Endocrinology
Trenbolone
Tubulin
Nandrolone
Testosterone
Cerebral Cortex
Neurons
Chemistry
Neurite outgrowth
Basic Medicine
medicine.anatomical_structure
Receptors, Androgen
030220 oncology & carcinogenesis
Molecular Medicine
Female
Trenbolone Acetate
medicine.drug
medicine.medical_specialty
Neurite
Medicinska och farmaceutiska grundvetenskaper
Cell Survival
Neuronal Outgrowth
Primary Cell Culture
03 medical and health sciences
Internal medicine
medicine
Neurotoxicity
Animals
Viability assay
Rats, Wistar
Molecular Biology
Dose-Response Relationship, Drug
Cell Biology
medicine.disease
Farmaceutiska vetenskaper
Androgen receptor
030104 developmental biology
Rat
Neuron
Stanozolol
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ae9d63366429cd56ba5aaef29eda23f8