Characterization of age-dependent changes in the striatum: Response to the mitochondrial toxin 3-nitropropionic acid

Publication date: Available online 30 April 2016 Source:Mechanisms of Ageing and Development Author(s): G.K. Shinomol, S. Ranganayaki, Apurva K. Joshi, N. Gayathri, Harsha Gowda, Muralidhara, Srinivas Bharath M.M. 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...
Source: Mechanisms of Ageing and Development - Category: Geriatrics Source Type: research