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About the Division

Mission

Identify/quantify neurotoxicity related to FDA-regulated products, develop and qualify quantitative biomarkers of neurotoxicity, and identify biological pathways associated with the expression of neurotoxicity to improve risk assessments and new approaches for diagnosis, as well as supporting the evolving needs of FDA product centers.

Ethnicity- and Gender-Related Differences in Alzheimer’s Disease

Watch the Recorded Presentation

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2021 Select Accomplishments

Cannabidiol Exposure and Its Effects

An emerging focus within FDA is developmental toxicity associated with cannabidiol (CBD). In collaboration with FDA’s Office of the Chief Scientist, DNT researchers began a multiple-year assessment of the effects of CBD early in life on brain development and cognitive performance in the rat. Additionally, researchers studied the possibility of early-life exposure to CBD altering the immune response later in life. These studies are expected to determine if the brain’s “defense mechanisms” against infection and injury change in response to these exposures. Work will continue into 2022 and will fill data gaps and guide future regulatory decisions.

Developmental Toxicity of Inorganic Arsenic Exposure

Arsenic occurs naturally in groundwater and can find its way into various foods including rice, a popular ingredient in baby foods. NCTR researchers collaborated with CFSAN to complete a comprehensive assessment of the neurotoxic potential of early-life exposure to arsenic. In these studies, rats were used to model the human response to arsenic exposure. The effects of arsenic on behavior and brain development were assessed and will soon be published. These data will help inform the Agency on acceptable levels of arsenic exposure from food in children.

Blood-Brain Barrier-Related Neurotoxicity 

The brain is a sensitive organ and exists in a micro-environment maintained by the blood-brain barrier (BBB). Failure of the BBB will compromise this micro-environment and can lead to brain damage. In collaboration with the Office of Women’s Health and NCTR’s Nanocore, DNT scientists investigated sex-linked differences in inflammation change in the BBB’s response to Alzheimer’s disease. Specifically, the impact of sex on BBB function, disease progression, and cognitive function were assessed. To complement these animal studies, "brain-on-a-chip" technology was used to better understand the mechanisms behind BBB dysfunction. The Division also took delivery of a new inverted live-cell imaging confocal microscope to enable assessments of BBB function and other neurotoxicity endpoints. 

Using Zebrafish Model to Explore Arsenic-Related Neurotoxicity 

The rat is a powerful and predictive research model but is slow compared to alternative research models. In collaboration with the NCTR-led Perinatal Health Center of Excellence (PHCE), researchers in the Division used the zebrafish to explore how arsenic causes neurotoxicity. This work will also allow the Division to assess the effectiveness of zebrafish for future toxicity assessments of other heavy metals. Using zebrafish may allow researchers to perform toxicities faster and at a lower cost. Preliminary findings from this work were presented at governmental workshops in 2021. 

Anesthesia-Related Neurotoxicity

The Division has been a leader in the field of developmental anesthesia-related neurotoxicity for over a decade. It is continuing this rich tradition by performing formal toxicity assessments, working to understand the conditions that lead to toxicity, and describing the mechanisms of toxicity. In collaboration with CDER, DNT scientists completed the experimental phase of an assessment of the neurotoxic potential of ketamine in a pediatric population. Moreover, the Division is using alternative assays to study the comparative toxicity of different anesthetic regimens and will soon begin studies to assess the interactions between cannabinoids and opioids on brain development. Through this work, the Division's goal is to understand the conditions needed for anesthesia-related neurotoxicity and to better define the risk associated with general anesthesia in a pediatric population. 

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Resources for You

• Division of Neurotoxicology Fact Sheet
• NCTR Grand Rounds: "Ethnicity- and Gender-Related Differences in Alzheimer’s Disease" (Presentation recorded in Adobe Connect on January 11, 2018)
• Annual Report
• NCTR Imaging Center
• Meet the Principal Investigators
• About the National Center for Toxicological Research

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