Expression pattern of ataxia telangiectasia mutated (ATM), p53, Akt, and glycogen synthase kinase-3β in the striatum of rats treated with 3-nitropropionic acid

Joaquim Duran-Vilaregut, Gemma Manich, Jaume del Valle, Antoni Camins, Mercè Pallàs, Jordi Vilaplana, Carme Pelegrí*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

3-Nitropropionic acid (3-NPA) is a mitochondrial toxin used in the laboratory to replicate neurodegenerative conditions that are accompanied by degeneration of the caudate-putamen. 3-NPA induces depletion in ATP production, reactive oxygen species production, and secondary excitotoxicity mediated by activation of N-methyl-D-aspartate receptors that culminates in the triggering of cell death mechanisms, including apoptosis. We here examined by immunohistochemical methods whether cellular expression of phosphoSer1981-ataxia telangiectasia mutated (ATM), phosphoSer15-p53, phosphoSer473-Akt, and phosphoSer9-glycogen synthase kinase-3β (GSK3β), which are key signal molecules that play a critical role in regulating cellular processes related to cell survival and demise, were involved in the striatal neurodegeneration in the brains of rats treated with 3-NPA. Our results indicate that the toxin induced the activation of ATM and p53 only in astrocytes, and a role for these proteins in neuronal degeneration was ruled out. On the other hand, striatal neurons lost the active form of Akt as soon as they began to appear pyknotic, indicating impairment of the PI3K/Akt/GSK3 pathway in their degenerative process. The inactive form of GSK3β was detected extensively, mainly in the rim of the striatal lesions around degenerating neurons, which could be attributed to a cell death or cell survival response.

Original languageAmerican English
Pages (from-to)1803-1813
Number of pages11
JournalJournal of Neuroscience Research
Volume90
Issue number9
DOIs
Publication statusPublished - Sep 2012

Keywords

  • Immunohistochemistry
  • Neurotoxin
  • Rat

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