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Biochemical, histopathological and behavioral alterations caused by intrastriatal administration of quinolic acid to young rats
Author(s) -
Pierozan Paula,
Fernandes Carolina G.,
Dutra Márcio F.,
Pandolfo Pablo,
Ferreira Fernanda,
Lima Bárbara O.,
Porciúncula Lisiane,
Wajner Moacir,
PessoaPureur Regina
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12762
Subject(s) - astrogliosis , quinolinic acid , excitotoxicity , striatum , neurodegeneration , hippocampus , glutamate receptor , neuroscience , endocrinology , medicine , psychology , central nervous system , biology , dopamine , disease , biochemistry , tryptophan , receptor , amino acid
Quinolinic acid ( QUIN ) is a neuroactive metabolite of the kinurenine pathway, and is considered to be involved in aging and some neurodegenerative disorders, including Huntington's disease. QUIN was injected intrastriatally into adolescent rats, and biochemical and histopathological analyses in the striatum, cortex, and hippocampus, as well as behavioral tests, were carried out in the rats over a period of 21 days after drug injection. Decreased [ 3 H ]glutamate uptake and increased 45 C a 2+ uptake were detected shortly after injection in the striatum and cerebral cortex. In the hippocampus, increased 45 C a 2+ uptake preceded the decreased [ 3 H ]glutamate uptake, without histopathological alterations. Also, corticostriatal astrogliosis was observed 7 days later, progressing to neuronal death at day 14. QUIN ‐treated rats also showed cognitive deficits 24 h after injection, concurrently with striatal astrogliosis. Motor deficits appeared later, after corticostriatal neurodegeneration. We assume that glutamate excitotoxicity could represent, at least in part, a molecular mechanism associated with the cognitive and motor impairments, corticostriatal astrogliosis and neuronal death observed in the QUIN ‐treated rats. We propose that our findings could be relevant for understanding the pathophysiology of human neurodegenerative diseases affecting young people, such as the juvenile form of H untington's disease, and for the design of potential therapeutic strategies to slow down the progression of the disease.