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Your Environment. Your Health.

University of Washington

Superfund Research Program

Cellular and Molecular Mechanisms of Cadmium Neurotoxicity

Project Leader: Zhengui Xia
Co-Investigators: Daniel Storm, Evan P. Gallagher
Grant Number: P42ES004696
Funding Period: 2015-2022
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2017-2022)

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. The investigators are exploring the molecular and cellular basis for the deleterious effects of Cd on olfaction and 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 dentate gyrus of the hippocampus and in olfactory bulb, and disrupts Ca2+signaling in neurons. They further hypothesize that these adverse cellular and molecular effects may underlie Cd neurotoxicity in cognition and olfaction.

This research project is testing these hypotheses both in primary cultured neural stem cells and in vivo in mice. These studies will provide new insights concerning mechanisms of Cd neurotoxicity, establish animal models to ascertain a causal relationship between Cd exposure and impairment in cognition and olfaction, and elucidate underlying cellular and molecular mechanisms. Their results may provide useful information for Cd risk.

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