Cadmium level in brain correlates with memory impairment in F1 and F2 generation mice: improvement with quercetin

Abstract

The increased exposure to cadmium (Cd) through environmental pollutants, food and cigarette smoke is a concern worldwide. The association of Cd with impaired learning disabilities led us to hypothesise that cadmium levels in brain tissue could be dose-dependently related to the extent of memory impairment and oxidative stress. In this study, we proposed to study whether cadmium exposure to dams could alter the brain Cd levels, memory parameters, antioxidant enzymes in brain and their gene expression in the F1-F2 generation mice and whether quercetin could modulate this effect. Animals were administered Cd alone and in combination with quercetin for 7 days during their gestation period. Their newborn pups (F1 and F2 mice) were reared until adulthood and were tested for memory using Morris water maze and step-down latency test. The brain tissue of F1 mice was collected. Cd levels were estimated using the atomic absorption spectrophotometer. G-S-transferase (GST) and catalase (CAT) activity were measured and fold increase in their respective gene expression was observed using the RT-PCR method. Cd levels were significantly increased in the brain tissue of animals exposed to Cd but cotreatment with quercetin showed decreased levels in both generations. Memory impairment was observed in animals of F1 generation exposed to Cd and cotreatment with quercetin (100 mg/kg) reversed this effect. Cd exposure significantly enhanced both activity and expression of GST and CAT in the brain tissue of F1 generation mice and quercetin attenuated this effect. In F2 generation, results were variable. GST activity and expression increased with Cd and decreased with quercetin cotreatment. However, CAT activity showed no significant change despite a decrease in gene expression. Quercetin cotreatment enhanced activity as well gene expression in F2 generation. Our study insinuates that Cd levels could act as a predictor of memory impairment and altered enzyme activity and gene expression in brain tissue. Quercetin helped to reduce Cd levels in brain tissue of F1 and F2 generation and modulated the antioxidant system of the cell by affecting expression of antioxidant enzymes at the transcription level.

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