title: Biochemical, histopathological and behavioral alterations caused by intrastriatal administration of quinolic acid to young rats.
abstract: 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)Ca(2+) uptake were detected shortly after injection in the striatum and cerebral cortex. In the hippocampus, increased (45)Ca(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 Huntington's disease, and for the design of potential therapeutic strategies to slow down the progression of the disease.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brasil.
authors.forename: Paula
authors.initials: P
authors.lastname: Pierozan
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Fernandes
authors.forename: Márcio F
authors.initials: MF
authors.lastname: Dutra
authors.forename: Pablo
authors.initials: P
authors.lastname: Pandolfo
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ferreira
authors.forename: Bárbara O
authors.initials: BO
authors.lastname: de Lima
authors.forename: Lisiane
authors.initials: L
authors.lastname: Porciúncula
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Regina
authors.initials: R
authors.lastname: Pessoa-Pureur
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D017378:Quinolinic Acid
keywords: astrogliosis; excitotoxicity; neurodegeneration; quinolinic acid; striatum