title: Rotenone-induced neurotoxicity in rat brain areas: a study on neuronal and neuronal supportive cells.
abstract: The present study was conducted to correlate rotenone-induced neurotoxicity with cellular and molecular modifications in neuronal and neuronal supportive cells in rat brain regions. Rotenone was administered (3, 6 and 12 μg/μl) intranigrally in adult male Sprague-Dawley rats. After the 7th day of rotenone treatment, specific protein markers for neuronal cells - tyrosine hydroxylase (TH), astroglial cells - glial fibrillary acidic protein (GFAP), microglial cells - CD11b/c, and Iba-1 were evaluated by immunoblotting and immunofluorescence in the striatum (STR) and mid brain (MB). Apoptotic cell death was assessed by caspase-3 gene expression. Higher doses of rotenone significantly lowered TH protein levels and elevated Iba-1 levels in MB. All the doses of rotenone significantly increased GFAP and CD11b/c protein in the MB. In STR, rotenone elevated GFAP levels but did not affect TH, CD11b/c and Iba-1 protein levels. Caspase-3 expression was increased significantly by all the doses of rotenone in MB but in STR only by higher doses (6 and 12 μg). It may be suggested that astroglial activation and apoptosis play an important role in rotenone-induced neurotoxicity. MB appeared as more sensitive than STR toward rotenone-induced cell toxicity. The astroglial cells emerged as more susceptible than neuronal and microglial cells to rotenone in STR.
authors.affiliation: Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow 226001, U.P., India.
authors.forename: S
authors.initials: S
authors.lastname: Swarnkar
authors.forename: P
authors.initials: P
authors.lastname: Goswami
authors.forename: P K
authors.initials: PK
authors.lastname: Kamat
authors.forename: I K
authors.initials: IK
authors.lastname: Patro
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: C
authors.initials: C
authors.lastname: Nath
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D039481:CD11b Antigen; D039521:CD11c Antigen; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D007306:Insecticides; D008840:Microfilament Proteins; D012333:RNA, Messenger; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3