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University of Washington

Superfund Research Program

Cellular and Molecular Mechanisms of Cadmium Neurotoxicity

Project Leader: Zhengui Xia
Grant Number: P42ES004696
Funding Period: 2015-2023
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2015-2017)

Cadmium (Cd) is a heavy metal of high interest to the Superfund Initiative. It has no known physiological function but is a neurotoxicant. Cd exposure is associated with cognitive and olfactory impairment in humans. However, little is known concerning the underlying molecular and cellular mechanisms. This project explores the molecular and cellular basis for the deleterious effects of Cd on cognition in mouse models, with a focus on its effects on adult neurogenesis and Ca2+ signaling critical for hippocampus-dependent memory. The researchers hypothesize that Cd interferes with adult neurogenesis in the hippocampus, and disrupts Ca2+ signaling in neurons critical for learning and memory. They further hypothesize that these adverse cellular and molecular effects may underlie Cd neurotoxicity in cognition.

The researchers are determining if Cd2+ inhibits hippocampal adult neurogenesis and hippocampus-dependent memory formation. They are also investigating the effect of Cd2+ on Ca2+ signaling in hippocampal neurons in vivo. The researchers are utilizing both primary cultured neural stem cells and in vivo mouse models. Studies are providing new insights concerning mechanisms of Cd neurotoxicity. Results may establish new mouse models to investigate Cd neurotoxicity and may shed lights regarding neurotoxicity of other heavy metals.

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