17β-Trenbolone Exposure Enhances Muscle Activity and Exacerbates Parkinson's Disease Progression in Male Mice.

Abstract

Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder, and while the neuroprotective effects of estrogen are well-documented, the impact of androgens on neurological disorders remains understudied. The consequences of exposure to 17-trenbolone (17-TB), an environmental endocrine disruptor with androgen-like properties, on the mammalian nervous system have received limited attention. Therefore, in this study, we aimed to investigate the biological effects of 17-TB exposure on PD. In our investigation using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we discovered that 17-TB exposure elevated testosterone hormone levels prevented androgen receptor (AR) reduction, upregulated the expression of muscular dystrophic factors (Atrogin1, MuRF1, Musa1, and Myostatin), improved muscle strength, and enhanced locomotor activity in the open field test. However, it is noteworthy that exposure to 17-TB also led to an upregulation of neuroinflammatory cytokines (NLRP3, IL-6, IL-1α, and IL-1β) in PD mice. Crucially, 17-TB exposure induced downregulation of nigral apoptotic proteins DJ-1 and Bcl-2 while upregulating Bax and Caspase-3 in PD mice. This exacerbated neuronal apoptosis, ultimately intensifying dopaminergic neuronal degeneration and death in the substantia nigra and striatum of PD mice. In conclusion, our findings indicate that while 17-TB mitigates muscle atrophy and enhances motor activity in PD mice, it concurrently exacerbates neuroinflammation, induces neuronal apoptosis, and worsens dopaminergic neuronal death, thereby aggravating the progression of MPTP-induced Parkinsonism. This underscores the importance of considering potential environmental risks in neurodegeneration associated with Parkinson's disease, providing a cautionary tale for our daily exposure to environmental endocrine chemical disruptors.