Abstract
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exacerbates mitochondrial impairment and α-synuclein expression leading to Parkinsonism. Impaired mitochondria and over-expressed α-synuclein are degraded and eliminated via macroautophagy and chaperone-mediated autophagy. Owing to multiple properties, silymarin protects from oxidative stress–mediated cellular injury. However, its effect on MPTP-induced changes in autophagy is not yet known. The study aimed to decipher the effect of silymarin on MPTP-induced changes in autophagy. Male mice (20–25 g) were treated with silymarin (intraperitoneally, daily, 40 mg/kg) for 2 weeks. On day 7, a few animals were also administered with MPTP (intraperitoneally, 20 mg/kg, 4 injections at 2-h interval) along with vehicles. Striatal dopamine content was determined. Western blot analysis was done to assess α-synuclein, beclin-1, sequestosome, phosphorylated 5′ adenosine monophosphate–activated protein kinase (p-AMPK), lysosome-associated membrane protein-2 (LAMP-2), heat shock cognate-70 (Hsc-70), LAMP-2A, phosphorylated unc-51-like autophagy activating kinase (p-Ulk1), and phosphorylated mechanistic target of rapamycin (p-mTOR) levels in the nigrostriatal tissue. Silymarin rescued from MPTP-induced increase in beclin-1, sequestosome, p-AMPK, and p-Ulk1 and decrease in LAMP-2, p-mTOR, and LAMP-2A levels. Silymarin defended against MPTP-induced increase in α-synuclein and reduction in dopamine content. The results demonstrate that silymarin protects against MPTP-induced changes in autophagy leading to Parkinsonism.
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Acknowledgments
We sincerely express our gratitude to the Department of Biotechnology, India, for rendering fellowship to the first author; Department of Science and Technology, India, to the second author; and Council of Scientific and Industrial Research, India, to the third author of the article. The CSIR-IITR communication number of this article is 3600.
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Manish Kumar Tripathi was involved in the data generation, acquisition, and analysis. Mohd Sami Ur Rasheed and Abhishek Kumar Mishra were involved in performing some initial experiments and treating the experimental animals if and when Manish Kumar Tripathi was on leave or busy in some other activities. Devendra Kumar Patel performed dopamine estimation. Mahendra Pratap Singh conceived the study plan and interpreted the analyzed data, which were provided by the first author. Manish Kumar Tripathi wrote the first version of the manuscript and Mahendra Pratap Singh revised the language. All authors have gone through the submitted version of the manuscript and endorsed the same.
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Tripathi, M.K., Rasheed, M.S.U., Mishra, A.K. et al. Silymarin Protects Against Impaired Autophagy Associated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinsonism. J Mol Neurosci 70, 276–283 (2020). https://doi.org/10.1007/s12031-019-01431-8
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DOI: https://doi.org/10.1007/s12031-019-01431-8