Superfund Research Program
Cellular and Molecular Mechanisms of Cadmium Neurotoxicity
Cadmium (Cd) is a heavy metal of high interest to the Superfund Research Program. Recent epidemiology studies have suggested a possible association between Cd exposure and cognitive, as well as olfactory, impairments in humans. However, studies in animal models were needed to establish a direct causal relationship between Cd exposure and impairments in cognition and olfaction. Project data from first and second years of funding indicate that Cd exposure induces impairment of hippocampus-dependent learning and memory in mice. However, the underlying mechanisms for this defect were not known. The goal of this project in the last funding cycle was to determine if Cd inhibits adult neurogenesis and to identify underlying signaling pathways responsible for this impairment. Adult hippocampal neurogenesis is a process in which adult neural progenitor/stem cells in the subgranular zone of the dentate gyrus generate functional new neurons in the hippocampus which contributes to hippocampus-dependent learning and memory. Recent results suggest that Cd exposure impairs adult hippocampal neurogenesis both in vitro and in vivo. This may contribute to Cd-mediated inhibition of hippocampus-dependent learning and memory (Toxicol Sci. 2019, PMID:31271426). In order to determine if Cd2+ interferes with Ca2+ signaling in hippocampal neurons in vivo in mice (Specific Aim 1), the research team developed a method to monitor Ca2+ signaling in CA3 hippocampal neurons in vivo in free-moving mice (PLoS One. 2019, PMID:31269057).