An area of needed exploration is environmentally-induced behavioral disorders. Studies show Cadmium (Cd) toxicity can manifest as behavioral disorders, cognitive challenges, and vision deficiencies in humans, but the pathway for these adverse effects is unknown. Its long biological half-life exacerbates the importance of understanding how early-life Cd exposure impacts later life outcomes and future generations. In this study, Dr. Delia Shelton proposes to test the hypothesis that chronic human dietary-relevant Cd exposure leads to visuo-behavioral disorders later in life and across generations. In the K99 mentored phase, she will expose zebrafish to chronic human-relevant dietary Cd concentrations and test for adverse visuo-behavioral effects, and then link this behavioral toxicity to neurophysiological and genetic endpoints (aim 1). This builds on her previous work developing automated technologies to assess environmental features that influence social behavior in wild and domestic zebrafish. She will advance her knowledge in developmental molecular toxicology, neuroscience, and bioinformatics used to expose, assess, and analyze the impact of Cd-induced behavioral disorders on behavior, brain, visual physiology and gene expression, through didactic instruction, seminars, conferences, extensive hands-on training, and guidance from a diverse advisory committee of respected researchers. This multifaceted training plan will complement her expertise in behavioral ecology by providing her with new skills in: 1) toxicology study design, 2) electrophysiology to assess the Cd?s impact on visual and central nervous systems, 3) molecular methods and bioinformatics used to identify genetic endpoints, and 4) advanced imaging methods to identify, quantify the accumulation of pollutants in tissues. In the R00 phase, Dr. Delia Shelton will initiate a new line of investigation to examine Cd-induced intergenerational and transgenerational behavioral disorders. By building on her training from the K99 phase she will identify novel behavioral, physiological, and genetic endpoints that predict intergenerational and transgenerational behavioral disorders (aim 2). Findings from these studies will improve our understanding of the mechanisms underlying the relationship between dietary cadmium exposure and visuo-behavioral disorders across generations and further elucidate environment-induced behavioral disease etiology. Characterizing the visuo-behavior, visual and central nervous system function, and gene expression in the context of dietary Cd exposure, has implications for prevention policy directed at reducing Cd exposure. The proposal provides an alternative model to meet modern challenges in chemical screening that better account for environment-induced behavioral disorders. With this proposed study, Dr. Shelton is well positioned to take advantage of existing resources to develop independent, yet complementary projects, designed to help fill critical gaps in our understanding of the impacts of Cd on behavioral disorders that may have far-reaching public health implications for psychiatric pathologies.
Cadmium is a near ubiquitous food contaminant that the general (non-occupational, non-smoking) population ingests at higher levels than the WHO determined provisional tolerable weekly intake. Cadmium is associated with impaired vision, learning challenges and behavioral disorders, with possible cascading effects on future generations. This proposal examines how cadmium exposure insults vision and genetic profiles leading to negative effects on learning, memory, and behavior in juveniles and across generations using zebrafish (Danio rerio) as a model, which supports NIEHS new initiative on Environmental Risks for Psychiatric Disorders.
