Journal
MOLECULAR NEUROBIOLOGY
Volume 53, Issue 8, Pages 5782-5795Publisher
SPRINGER
DOI: 10.1007/s12035-015-9478-6
Keywords
Zinc; Inflammation; Oxidative stress; Neurodegeneration; Apoptosis
Categories
Funding
- Council of Scientific and Industrial Research (CSIR), New Delhi
- Department of Biotechnology, New Delhi
- Department of Science and Technology
- CSIR-network program neurodegenerative diseases: causes and corrections (miND) [BSC0115]
Ask authors/readers for more resources
Clinical evidences showing zinc (Zn) accumulation in the post-mortem brain of Parkinson's disease (PD) patients and experimental studies on rodents chronically exposed to Zn suggested its role in PD. While oxidative stress is implicated in Zn-induced neurodegeneration, roles of inflammation and apoptosis in degeneration of the nigrostriatal dopaminergic neurons have yet been elusive. The present study investigated the contribution of the nuclear factor kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and B-cell lymphoma 2 (Bcl-2) family proteins in Zn-induced Parkinsonism. Male Wistar rats were treated with/without zinc sulfate (Zn; 20 mg/kg, intraperitoneally), twice a week, for 2-12 weeks. In a few sets, animals were treated intraperitoneally with a NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC; 100 mg/kg), a TNF-alpha inhibitor, pentoxyfylline (PTX; 50 mg/kg), and an anti-inflammatory agent, dexamethasone (DEX; 5 mg/kg), prior to Zn exposure along with respective controls. Zn caused neurobehavioral impairments and reduction in dopamine and its metabolites, tyrosine hydroxylase (TH)-positive neurons, catalase activity, and expression of TH, Bcl-2, and NOXA. On the contrary, Zn augmented lipid peroxidation, activity of superoxide dismutase, expression of TNF-alpha, IL-1 beta, Bcl-xl, and p53-upregulated modulator of apoptosis (PUMA), and translocation of NF-kappa B and Bax from the cytosol to the nucleus and mitochondria, respectively, with concomitant increase in the mitochondrial cytochrome c release and activation of procaspase-3 and -9. Pre-treatment with PTX, DEX, or PDTC invariably ameliorated Zn-induced changes in behavioral and neurodegenerative indexes, inflammatory mediators, and apoptosis. Results demonstrate that inflammation regulates Bax expression that subsequently contributes to the nigrostriatal dopaminergic neurodegeneration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available