title: Nigrostriatal proteomics of cypermethrin-induced dopaminergic neurodegeneration: microglial activation-dependent and -independent regulations.
abstract: The study aimed to identify the differentially expressed nigrostriatal proteins in cypermethrin-induced neurodegeneration and to investigate the role of microglial activation therein. Proteomic approaches were used to identify the differentially expressed proteins. Microglial activation, tyrosine hydroxylase immunoreactivity (TH-IR), dopamine content, and neurobehavioral changes were measured according to the standard procedures. The expressions of α-internexin intermediate filament (α-IIF), ATP synthase D chain (ATP-SD), heat shock protein (Hsp)-70, truncated connexin-47, Hsp-60, mitogen-activated protein kinase-activated kinase-5, nicotinamide adenine dinucleotide dehydrogenase 24k chain precursor, platelet-activating factor acetyl hydrolase 1b-α2 (PAF-AH 1b-α2), and synaptosomal-associated protein-25 (SNAP-25) were altered in the substantia nigra and nicotinamide adenine dinucleotide- specific isocitrate dehydrogenase, phosphatidylethanolamine-binding protein-1, prohibitin, protein disulfide isomerase-endoplasmic reticulum 60 protease, stathmin, and ubiquitin-conjugating enzyme in the striatum along with motor impairment, decreased dopamine and TH-IR, and increased microglial activation after cypermethrin exposure. Minocycline restored α-IIF, ATP-SD chain, truncated connexin-47, Hsp-60, PAF-AH 1b-α2, stathmin and SNAP-25 expressions, motor impairment, dopamine, TH-IR, and microglial activation. The results suggest that cypermethrin produces microglial activation-dependent and -independent changes in the expression patterns of the nigrostriatal proteins leading to dopaminergic neurodegeneration.
authors.affiliation: Council of Scientific and Industrial Research, Indian Institute of Toxicology Research-Council of Scientific and Industrial Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India. singhmahendrapratap@rediffmail.com
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Manindra Nath
authors.initials: MN
authors.lastname: Tiwari
authors.forename: Anubhuti
authors.initials: A
authors.lastname: Dixit
authors.forename: Ghanshyam
authors.initials: G
authors.lastname: Upadhyay
authors.forename: Devendra Kumar
authors.initials: DK
authors.lastname: Patel
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Singh
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002853:Chromatography, Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000032:analysis; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology*; D010641:Phenotype; D040901:Proteomics / Q000379:methods*; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; D011722:Pyrethrins; C046643:alpha-internexin; C017160:cypermethrin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine