Mentor(s): Anna Radke

Lead is a naturally occurring element that is found in paint, gasoline, and plumbing. It is also recognized as a potent neurotoxin that accumulates in the body and disrupts normal brain development and functioning (Rice, 1996). Exposure is linked to reduced IQ, behavioral issues, and cognitive impairment (Ortega et al., 2021). Lead crosses the placental and blood-brain barriers, which makes fetuses and young children particularly vulnerable to the adverse effects. Adolescents have a critical window of brain development, during which exposure to neurotoxicants can produce detrimental effects on learning, memory, and overall cognitive function. Even low levels, <5 µg/dL, have been linked to cognitive and behavioral dysfunction. It is estimated that the number of children in the US with Blood Lead Levels (BLLs) 10>g/dL, which is twice the current CDC blood lead reference value, is between 123-269 thousand (Albores-Garcia et al., 2021).

Learning and memory are two specific functions that have been shown to be impacted by even low levels of lead exposure. The hippocampus, the brain region critical for memory formation and learning processes, has shown disruptions in synaptic plasticity and neuronal loss from lead exposure (Oliveira et al., 2020). Lead has been shown to accumulate in the hippocampus from adolescent exposure, which triggers oxidative stress and leads to widespread dysfunction of critical proteins such as NLGN1, a protein required for synaptogenesis, dendritic spine maturation and stability in the hippocampus (Zhao et al., 2018). These dysfunctions are thought to impact long term potentiation, a key cellular mechanism for forming memories. This is presumed to be the biological mechanism behind lead’s demonstrated negative influence on learning and memory (Wang et al., 2016; Rice, 1996; Oliveira et al., 2020; Anderson et al., 2016; Shvachiy et al., 2022).

Lead causes oxidative stress through its ability to catalyze oxidative reactions and generate reactive oxygen species (ROS) (Patrick, 2006). ROS are a type of free radical: unstable molecules with an unpaired electron, and can cause damage in large amounts from their propensity to react with important nearby molecules in order to achieve stability. The generation of ROS and depletion of antioxidant reserves are postulated to be the underlying mechanism of many of the detrimental effects and diseases caused by lead exposure, including within the hippocampus (Oliveira et al., 2020).

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