Similarities in lindane induced alterations in protein expression profiling in different brain regions with neurodegenerative diseases.
Previous studies have reported that lindane, an organochlorine pesticide induces oxidative stress in rat brain that may lead to neurodegeneration. However, as the proteins involved in lindane induced neurodegeneration are yet to be identified, the present study aims to identify the proteins that may regulate lindane induced neurotoxicity. The data showed that repeated exposure of lindane (2.5 mg/kg) for 21 days to adult rats significantly increased the reactive oxygen species and lipid peroxidation in different brain regions. Proteomic study revealed that lindane induces major dysregulation in the ubiquitin proteasome pathway. Alterations in the expression of molecular chaperones in brain regions and an increase in the expression of α-synuclein in substantia-nigra and corpus-striatum and amyloid precursor protein in hippocampus and frontal-cortex suggests the accumulation of proteins in these brain regions. Western blotting also revealed alterations in the dopaminergic and cholinergic pathways in hippocampus and substantia-nigra isolated from lindane treated rats. Neurobehavioural data indicating alterations in learning and working memory, conditioned avoidance response and motor function, supports the proteomic data. The data suggest that repeated exposure of lindane to adult rats induces alterations, which are similar to that seen in neurodegenerative diseases.
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.|Academy of Scientific & Innovative Research, CSIR-IITR Campus, Lucknow, India.
Anubha
A
Mudawal
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.
Anshuman
A
Singh
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.|Academy of Scientific & Innovative Research, CSIR-IITR Campus, Lucknow, India.
Sanjay
S
Yadav
Plant Molecular Biology Laboratory, CSIR-National Botanical Research Institute (CSIR-NBRI), Lucknow, India.
Manisha
M
Mishra
Plant Molecular Biology Laboratory, CSIR-National Botanical Research Institute (CSIR-NBRI), Lucknow, India.
Pradhyumna Kumar
PK
Singh
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.
Lalit Pratap
LP
Chandravanshi
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.
Juhi
J
Mishra
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.|Academy of Scientific & Innovative Research, CSIR-IITR Campus, Lucknow, India.
Vinay K
VK
Khanna
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.|Academy of Scientific & Innovative Research, CSIR-IITR Campus, Lucknow, India.
Sanghamitra
S
Bandyopadhyay
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India.|Academy of Scientific & Innovative Research, CSIR-IITR Campus, Lucknow, India.
Devendra
D
Parmar
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology; D018384:Oxidative Stress / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D010575:Pesticides; D020543:Proteome; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D001556:Hexachlorocyclohexane; D002374:Catalase; D013482:Superoxide Dismutase; D046988:Proteasome Endopeptidase Complex; D005978:Glutathione
Animal Proteomics; Brain regions; Lindane; Neurobehaviour; Proteomic analysis; Rat; Western blotting