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

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Relation http://ir.cftri.com/13391/
http://dx.doi.org/10.1016/j.mad.2016.04.008
 
Title Characterization of age-dependent changes in the striatum: Response
to the mitochondrial toxin 3-nitropropionic acid.
 
Creator Shinomol, George K.
Ranganayaki, S.
Apurva, K. Joshi
Gayathri, N.
Harsha, Gowda
Dr., Muralidhara
 
Subject 03 Biochemistry & Molecular Biology
 
Description tNeurodegenerative phenomena are associated with mitochondrial dysfunction and this could be exac-erbated by aging. Age-dependence of mitochondrial response to toxins could help understand thesemechanisms and evolve novel therapeutics. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin thatinduces neurotoxicity in the striatum via inhibition of complex II. We investigated the age-related eventsthat contribute to 3-NPA toxicity. 3-NPA induced neuronal death, oxidative stress and altered mito-chondrial structure in neuronal cells. 3-NPA injection in vivo caused motor impairment, mitochondrialdysfunction 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 youngmice (control: YC vs. 3-NPA treated: YT) and adult mice (control: AC vs. 3-NPA treated: AT). Among the3752 identified proteins, 33 differentially expressed proteins (mitochondrial, synaptic and microsomalproteins) were unique either to YT or AT. Interestingly, comparison of the proteomic profile in AC andYC 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. Wesurmise that aging contributes to the cellular and molecular architecture in the mouse striatum withimplications for neurodegeneration.
 
Date 2017
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/13391/1/Mechanisms%20of%20Ageing%20and%20Development%20xxx%20%282016%29.pdf
Shinomol, George K. and Ranganayaki, S. and Apurva, K. Joshi and Gayathri, N. and Harsha, Gowda and Dr., Muralidhara (2017) Characterization of age-dependent changes in the striatum: Response to the mitochondrial toxin 3-nitropropionic acid. Mechanisms of Ageing and Development, 161. pp. 66-82.