Proteomic approaches to investigate age related vulnerability to lindane induced neurodegenerative effects in rats

• Published in: Food and chemical toxicology 2018-05, Vol.115, p.499-510
• Main Authors: Mudawal, Anubha, Srivastava, Ankita, Singh, Anshuman, Shankar, Jai, Yadav, Sanjay, Mishra, Manisha, Singh, Pradhyumna K., Khanna, Vinay K., Parmar, Devendra
• Format: Article
• Language: English
• Subjects: Age; Age Factors; Animals; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; Autophagy - drug effects; Blotting, Western; Brain; Electrophoresis, Gel, Two-Dimensional; Glutathione - metabolism; Hexachlorocyclohexane - toxicity; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - ultrastructure; Insecticides - toxicity; Lindane; Lipid Peroxidation - drug effects; Male; Microscopy, Electron, Transmission; Molecular Chaperones - metabolism; Nerve Tissue Proteins - metabolism; Oxidative stress; Oxidative Stress - drug effects; Proteomics; Rats, Wistar; Reactive Oxygen Species - metabolism; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - ultrastructure
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2018.03.049

Proteomic studies were carried out in immature (3 week), adult (18 week) and aged (48 week) rats to understand the age dependent vulnerability to lindane induced neurodegeneration. 2-D and western blot analysis of protein extracts of hippocampus and substantia-nigra isolated from lindane treated rats (2.5 mg/kg; p.o. X 21 days) revealed marked dysregulation in the expression of proteins related to ubiquitin proteasome pathway, antioxidant activity, chaperones, energy metabolism, calcium homeostasis and proteins involved in neurodegeneration. These alterations were associated with marked increase in reactive oxygen species formation, lipid peroxidation, reduced glutathione content and antioxidant enzyme activities in lindane treated rats. Aged rats, in particular showed higher magnitude of alteration in these proteins when compared to immature or adult rats. Proteins involved in apoptosis and autophagy also showed marked alterations in their expression, particularly in the aged rats. Ultrastructural analysis revealed greater number of autophagic vesicle in hippocampus and substantia-nigra in treated aged rats. The data suggest that proteomic approaches could be used to investigate the vulnerability to lindane induced neurodegeneration in rats. •Lindane induced oxidative stress in rats of different ages led to apoptosis and disruption of autophagy in brain regions.•The role of proteins involved in lindane induced neurotoxicity was identified.•Aged rats exhibited enhanced vulnerability to lindane induced neurodegeneration.