Neurobehavioral Deficits Linked to Manganese Exposure

Studies in children and adolescents have linked developmental environmental manganese (Mn) exposure to inattention, impulsivity, hyperactivity, oppositional behaviors, and fine motor deficits.

Barbara Strupp, Nutritional Sciences, in collaboration with researchers at University of California, Santa Cruz, is using a rodent model of pediatric Mn exposure to identify clinically relevant therapies and to explain the underlying neural mechanisms of this health concern.

The group’s recent studies have shown that developmental Mn exposure causes lasting deficits in attention, impulse control, and fine motor function in a rodent model— providing the first causal evidence that supports the associations reported in human studies. These effects are associated with lasting changes in the catecholaminergic system in the prefrontal cortex and striatum brain areas, including reductions in dopamine and norepinephrine release and altered levels of cellular transporters and receptors for these neurotransmitters. This is akin to the hypofunctioning catecholaminergic system in children with attentional and impulse control deficits.

Initial studies have demonstrated the potential benefits of chronic oral methylphenidate (Ritalin) treatment for alleviating the Mn-induced impulse control and fine motor dysfunctions. Because this treatment, however, did not improve the attentional dysfunction, further studies are needed to identify a more effective treatment. This grant funds studies to investigate other therapeutic approaches, as well as further elucidate the neural mechanisms underlying the lasting attentional, impulse control, and fine motor dysfunction caused by developmental Mn exposure.

This knowledge will inform public health policies and guidelines on suitable levels of manganese exposure to children, and improve therapies for exposed individuals.

NIH Award Number: 1R01ES028369-01A1

Cornell Researchers

Funding Received

$646 Thousand spanning 5 years