title: Characterization of age-dependent changes in the striatum: Response to the mitochondrial toxin 3-nitropropionic acid.
abstract: Neurodegenerative phenomena are associated with mitochondrial dysfunction and this could be exacerbated by aging. Age-dependence of mitochondrial response to toxins could help understand these mechanisms and evolve novel therapeutics. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that induces neurotoxicity in the striatum via inhibition of complex II. We investigated the age-related events that contribute to 3-NPA toxicity. 3-NPA induced neuronal death, oxidative stress and altered mitochondrial structure in neuronal cells. 3-NPA injection in vivo caused motor impairment, mitochondrial dysfunction and oxidative damage with different trend in young and adult mice. To understand the age-dependent mechanisms, we carried out proteomic analysis of the striatal protein extract from young mice (control: YC vs. 3-NPA treated: YT) and adult mice (control: AC vs. 3-NPA treated: AT). Among the 3752 identified proteins, 33 differentially expressed proteins (mitochondrial, synaptic and microsomal proteins) were unique either to YT or AT. Interestingly, comparison of the proteomic profile in AC and YC indicated that 161 proteins (linked with cytoskeletal structure, neuronal development, axogenesis, protein transport, cell adhesion and synaptic function) were down-regulated in AC compared to YC. We surmise that aging contributes to the cellular and molecular architecture in the mouse striatum with implications for neurodegeneration.
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India; Neurotoxicology laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India.
authors.forename: G K
authors.initials: GK
authors.lastname: Shinomol
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India; Neurotoxicology laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India.
authors.forename: S
authors.initials: S
authors.lastname: Ranganayaki
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India; Neurotoxicology laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India.
authors.forename: Apurva K
authors.initials: AK
authors.lastname: Joshi
authors.affiliation: Department of Neuropathology, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India.
authors.forename: N
authors.initials: N
authors.lastname: Gayathri
authors.affiliation: Institute of Bioinformatics (IOB), Discoverer, Industrial Technology Park Limited (ITPL), Whitefield, Bangalore 560066, Karnataka, India.
authors.forename: Harsha
authors.initials: H
authors.lastname: Gowda
authors.affiliation: Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570020, Karnataka, India.
authors.lastname: Muralidhara
authors.affiliation: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India; Neurotoxicology laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, 2900, Hosur Road, Bangalore 560029, Karnataka, India. Electronic address: harath@nimhans.ac.in.
authors.forename: M M
authors.initials: MM
authors.lastname: Srinivas Bharath
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D042963:Electron Transport Complex II; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009574:Nitro Compounds / Q000009:adverse effects* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011422:Propionates / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats
chemical_list: D024101:Mitochondrial Proteins; D009574:Nitro Compounds; D011422:Propionates; D042963:Electron Transport Complex II; C015392:3-nitropropionic acid
keywords: 3-NPA; Brain aging; Mitochondria; Proteomics; Striatum