Manganese Exposure Windows

Manganese Exposure Windows And Neurologic Function In Adolescence

Drs. Roberto Lucchini and Robert Wright have been the primary investigators of the Manganese Exposure Windows and Neurologic Function In Adolescence project since their $2.5 million award was presented to them to study and characterize the effects of environmental manganese (Mn) exposure on adolescent neurodevelopment. Although long known to be a critical neurodevelopmental period in pediatrics/psychology, little is known about the impact of toxic chemical exposures on neurophenotypes in adolescence.

roberto-lucchini-md“Mn is a compelling neurotoxicant to study in adolescence because it’s an essential trace metal, but it is also neurotoxic at elevated exposures; the catecholaminergic system is a well-known target of Mn, and adolescence neurodevelopment involves substantial changes to the dopaminergic system, Mn exposure is more ubiquitous than previously recognized, but its role in altering brain development is not well known, and there are significant knowledge gaps regarding the impacts of Mn in adolescence.”

– Roberto Lucchini, MD

Preliminary results from our initial grant period show that elevated Mn exposure during pre/early adolescence is associated with deficits in attention, neuromotor, cognitive, and olfactory function in children. We have built upon these findings in a cohort of 240 adolescents to determine: 1) the role of Mn exposure timing on adolescent executive function, behavior, and self-regulation by applying novel exposure biomarkers and statistical methods to identify and define critical developmental windows of susceptibility, and 2) functional and anatomical neurophenotypes that are impacted by Mn, focusing on brain areas that subserve executive function, behavior, and self-regulation in adolescence (e.g., Pre-Frontal Cortex, ventral striatum, amygdala) using functional and anatomical MRI.

Our established PHIME (Public Health Impact of Manganese Exposure) cohort presents a unique opportunity to achieve these important goals. PHIME was designed to investigate long-term Mn exposure timing; it consists of subjects (now adolescents) living in three well-characterized communities in Northern Italy that differ in the timing and intensity of environmental Mn exposure from current or historic ferromanganese alloy plant operations. Moreover, recent innovations in exposure science now allow us to retrospectively reconstruct Mn exposure across fetal life/early childhood using a novel tooth biomarker of exposure. These studies will be among the first to longitudinally assess the role of environmental Mn on adolescent neurodevelopment and behavior and to objectively determine critical exposure windows that can inform the timing of future public health interventions.

Publications associated with this grant:

Title: Hair as a biomarker of environmental manganese exposure
Authors: Eastman, Rachel R; Jursa, Tom P; Benedetti, Chiara; Lucchini, Roberto G; Smith, Donald R

Title: Impact of ferromanganese alloy plants on household dust manganese levels: implications for childhood exposure
Authors: Lucas, E L; Bertrand, P; Guazzetti, S; Donna, F; Peli, M; Jursa, T P; Lucchini, Roberto G; Smith, D R

Title: Inverse association of intellectual function with very low blood lead but not with manganese exposure in Italian adolescents
Authors: Lucchini, Roberto G; Zoni, Silvia; Guazzetti, Stefano; Bontempi, Elza; Micheletti, Serena; Broberg, Karin; Parrinello, Giovanni; Smith, Donald R

Title: Manganese concentrations in soil and settled dust in an area with historic ferroalloy production 
Authors: Pavilonis, Brian T; Lioy, Paul J; Guazzetti, Stefano; Bostick, Benjamin C; Donna, Filippo; Peli, Marco; Zimmerman, Neil J; Bertrand, Patrick; Lucas, Erika; Smith, Donald R; Georgopoulos, Panos G; Mi, Zhongyuan; Royce, Steven G; Lucchini, Roberto G

Title: Metal contamination of home garden soils and cultivated vegetables in the province of Brescia, Italy: implications for human exposure 
Authors: Ferri, Roberta; Hashim, Dana; Smith, Donald R; Guazzetti, Stefano; Donna, Filippo; Ferretti, Enrica; Curatolo, Michele; Moneta, Caterina; Beone, Gian Maria; Lucchini, Roberto G

Title: Metal fractionation in soils and assessment of environmental contamination in Vallecamonica, Italy
Authors: Borgese, L; Federici, S; Zacco, A; Gianoncelli, A; Rizzo, L; Smith, D R; Donna, F; Lucchini, Roberto G; Depero, L E; Bontempi, E

Title: Neurofunctional dopaminergic impairment in elderly after lifetime exposure to manganese 
Authors: Lucchini, Roberto G; Guazzetti, Stefano; Zoni, Silvia; Benedetti, Chiara; Fedrighi, Chiara; Peli, Marco; Donna, Filippo; Bontempi, Elza; Borgese, Laura; Micheletti, Serena; Ferri, Roberta; Marchetti, Serena; Smith, Donald R

Title: Tremor, olfactory and motor changes in Italian adolescents exposed to historical ferro-manganese emission
Authors: Lucchini, Roberto G; Guazzetti, Stefano; Zoni, Silvia; Donna, Filippo; Peter, Stephanie; Zacco, Annalisa; Salmistraro, Marco; Bontempi, Elza; Zimmerman, Neil J; Smith, Donald R