Sensory Mechanisms of Cadmium-Induced Behavioral Disorders Across Generations - Project Summary/Abstract
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.
