Chronic Developmental Manganese Exposure Affects Behavioral Phenotypes in Dopamine Transporter Mutant Mice

Overview

Overexposure to manganese (Mn) through contaminated water or occupational environment has been shown to result in dopaminergic dysfunction and overall neurotoxicity in the human brain [1]. The synaptic dopamine (DA) system primarily drives motivation, attention, and behavioral learning. Disruptions to dopaminergic signaling via the DA transporter (DAT) can play a causal role in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) development [2]. In mice, the DAT mutation T356M closely reflects behavioral indicators of autism and ADHD, such as repetitive behaviors, loss of social novelty, and hyperlocomotion [1]. Additionally, excess manganese intake in mice is positively correlated with dopamine dysfunction [2], and exposure to manganese during adolescence can drive expression of a hyperactive phenotype [3]. Groups of wild type and heterozygous DAT T356M mice were exposed to excess dietary manganese and compared to mice that received a control diet. Locomotor activity and spontaneous behavioral assessments were recorded and post-mortem brain levels of manganese, DAT, and tyrosine hydroxylase (TH) were analyzed [4]. Results from locomotor activity assessments show that male mice exposed to a high Mn diet become generally more hyperactive, while females become generally more hypoactive. Additionally, spontaneous behavior assessments demonstrated that the effects of high-Mn supplementation diminish over time, which could be attributed to age or homeostatic adaptations. Finally, these findings suggest that genotype effects may decrease with maturation.

Competition history

• ISEF 2024 Behavioral and Social Sciences · Entry BEHA035 · Los Angeles, California, United States

Resources

• ISEF abstract page ↗

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