The primary objectives of this study are to 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. Mn is a compelling neurotoxicant to study in adolescence because: i) Mn is an essential trace metal, but it is also neurotoxic at elevated exposures; ii) th catecholaminergic system is a well-known target of Mn, and adolescence neurodevelopment involves substantial changes to the dopaminergic system, iii) Mn exposure is more ubiquitous than previously recognized, but its role in altering brain development is not well known, and iv) there are significant knowledge gaps regarding the impacts of Mn in adolescence. 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 will build 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.
Adolescence may be a critical developmental window for chemical exposures and brain development. Manganese is a strong candidate toxicant to study with regards to adolescent development as it impacts dopaminergic systems known to undergo profound changes in the teenage years. This study will address the mechanisms by which environmental chemicals may impact adolescent brain development and can help explain and prevent maladaptive development from occurring, by potentially identifying future interventions to mitigate the impact of chemicals on the adolescent brain.
| Lucchini, Roberto G; Aschner, Michael; Landrigan, Philip J et al. (2018) Neurotoxicity of manganese: Indications for future research and public health intervention from the Manganese 2016 conference. Neurotoxicology 64:1-4 |
| Riva, Michele Augusto; Belingheri, Michael; De Vito, Giovanni et al. (2018) Bernardino Ramazzini (1633-1714). J Neurol 265:2164-2165 |
| Wahlberg, Karin; Arora, Manish; Curtin, Austen et al. (2018) Polymorphisms in manganese transporters show developmental stage and sex specific associations with manganese concentrations in primary teeth. Neurotoxicology 64:103-109 |
| Butler, Lindsey; Gennings, Chris; Peli, Marco et al. (2018) Assessing the contributions of metals in environmental media to exposure biomarkers in a region of ferroalloy industry. J Expo Sci Environ Epidemiol : |
| Bauer, Julia Anglen; Claus Henn, Birgit; Austin, Christine et al. (2017) Manganese in teeth and neurobehavior: Sex-specific windows of susceptibility. Environ Int 108:299-308 |
| Chiu, Yueh-Hsiu Mathilda; Claus Henn, Birgit; Hsu, Hsiao-Hsien Leon et al. (2017) Sex differences in sensitivity to prenatal and early childhood manganese exposure on neuromotor function in adolescents. Environ Res 159:458-465 |
| Lucchini, Roberto; Placidi, Donatella; Cagna, Giuseppa et al. (2017) Manganese and Developmental Neurotoxicity. Adv Neurobiol 18:13-34 |
| Austin, Christine; Richardson, Cardius; Smith, Donald et al. (2017) Tooth manganese as a biomarker of exposure and body burden in rats. Environ Res 155:373-379 |
| Wahlberg, Karin; Kippler, Maria; Alhamdow, Ayman et al. (2016) Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function. Toxicol Sci 149:473-83 |
| Iannilli, Emilia; Gasparotti, Roberto; Hummel, Thomas et al. (2016) Effects of Manganese Exposure on Olfactory Functions in Teenagers: A Pilot Study. PLoS One 11:e0144783 |
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