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Expression pattern of ataxia telangiectasia mutated (ATM), p53, Akt, and glycogen synthase kinase‐3β in the striatum of rats treated with 3‐nitropropionic acid
Author(s) -
DuranVilaregut Joaquim,
Manich Gemma,
del Valle Jaume,
Camins Antoni,
Pallàs Mercè,
Vilaplana Jordi,
Pelegrí Carme
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23060
Subject(s) - protein kinase b , excitotoxicity , neurodegeneration , gsk 3 , biology , gsk3b , microbiology and biotechnology , glycogen synthase , programmed cell death , striatum , ataxia telangiectasia , kinase , phosphorylation , apoptosis , neuroscience , biochemistry , medicine , dopamine , dna damage , disease , dna
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 phospho Ser1981 ‐ataxia telangiectasia mutated (ATM), phospho Ser15 ‐p53, phospho Ser473 ‐Akt, and phospho Ser9 ‐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. © 2012 Wiley Periodicals, Inc.