Intraventricular infusion of quinolinic acid impairs spatial learning and memory in young rats: a novel mechanism of lead-induced neurotoxicity.
J Neuroinflammation
; 15(1): 263, 2018 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-30217162
ABSTRACT
BACKGROUND:
Lead (Pb), a heavy metal, and quinolinic acid (QA), a metabolite of the kynurenine pathway of tryptophan metabolism, are known neurotoxicants. Both Pb and QA impair spatial learning and memory. Pb activates astrocytes and microglia, which in turn induce the synthesis of QA. We hypothesized increased QA production in response to Pb exposure as a novel mechanism of Pb-neurotoxicity.METHODS:
Two experimental paradigms were used. In experiment one, Wistar rat pups were exposed to Pb via their dams' drinking water from postnatal day 1 to 21. Control group was given regular water. In the second protocol, QA (9 mM) or normal saline (as Vehicle Control) was infused into right lateral ventricle of 21-day old rats for 7 days using osmotic pumps. Learning and memory were assessed by Morris water maze test on postnatal day 30 or 45 in both Pb- and QA-exposed rats. QA levels in the Pb exposed rats were measured in blood by ELISA and in the brain by immunohistochemistry on postnatal days 45 and 60. Expression of various molecules involved in learning and memory was analyzed by Western blot. Means of control and experimental groups were compared with two-way repeated measure ANOVA (learning) and t test (all other variables).RESULTS:
Pb exposure increased QA level in the blood (by ~ 58%) and increased (p < 0.05) the number of QA-immunoreactive cells in the cortex, and CA1, CA3 and dentate gyrus regions of the hippocampus, compared to control rats. In separate experiments, QA infusion impaired learning and short-term memory similar to Pb. PSD-95, PP1, and PP2A were decreased (p < 0.05) in the QA-infused rats, whereas tau phosphorylation was increased, compared to vehicle infused rats.CONCLUSION:
Putting together the results of the two experimental paradigms, we propose that increased QA production in response to Pb exposure is a novel mechanism of Pb-induced neurotoxicity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Quinolínico
/
Intoxicação do Sistema Nervoso por Chumbo
/
Aprendizagem Espacial
/
Transtornos da Memória
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neuroinflammation
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Kuait