Exposure to toxic metals and other environmental chemicals is a known cause of adverse health outcomes. Arsenic, for instance, poses a pervasive threat to respiratory health in both environmental and occupational settings. Epidemiologic and experimental studies link low-to-moderate arsenic exposure to reduced lung function, interstitial lung changes visible on imaging, and elevated cancer risk—effects that can be intensified by co-exposures like endotoxin or benzo[a]pyrene. Furthermore, recent research highlights the critical role of post-transcriptional modifications in regulating RNA metabolism, with aberrant epitranscriptomic regulation contributing to various human diseases. This symposium will explore the intersection of toxicant exposure and epitranscriptomic mechanisms, examining their implications for lung, cardiovascular, and neurodegenerative disorders. By connecting exposure assessment, mechanistic targets, biomarkers, and prevention strategies, the presentations aim to inform approaches for reducing environment-induced disease.

• 10:00–10:20am — The eNAMPT–TLR4 danger signal in arsenic-primed lung fibrosisJoe GN Garcia
• 10:20–10:40am — NRF2 preserves lung barrier integrity and mitigates arsenic-induced pulmonary inflammationDonna Zhang
• 10:40–11:00am — Microplastics, plastic-associated EDCs, and cardiovascular diseaseChangcheng Zhou
• 11:00–11:20am — Complete decoding of tsRNA modifications reveals structural and functional principlesQi Chen

Chronic inflammation is a crucial process involved in metal-induced neurotoxicity. Exposure to metals such as lead, tungsten, mercury, and manganese have all been linked to systemic and neurological inflammation, in several studies conducted with different animal systems, and in vitro approaches. It is also a well-known fact that neuroinflammation, inflammation within the central nervous system (CNS), is highly associated with several neurological disorders both of developmental and degenerative nature and is an important mechanistic aspect of metal-induced neurological conditions. The mechanisms by which metals can evoke chronic inflammation within the nervous system and other organs, are diverse and require further investigation towards efforts in mitigating the neurotoxic effects of exposures. This symposium will bring together researchers to present their substantial work on the effects of lead, tungsten, and manganese in dysregulation of inflammatory and neuroinflammatory mechanisms.

• 11:30–11:50am — Immune-mediated responses to inhaled tungsten particles and cardiac injuryAlicia Bolt
• 11:50am–12:10pm — Lead(Pb)-induced neuroinflammation in the developing zebrafish brainJennifer Freeman
• 12:10–12:30pm — Peripheral HIF-2 deficiency attenuates manganese-induced motor deficits independent of brain Mn loadNishant Sharma
• 12:30–12:50pm — Blood magnesium level and its metabolomic signatures are associated with lower risk of liver cancer compared to both no liver disease and liver disease controlsXuehong Zhang

Manganese (Mn) and iron (Fe) are essential trace elements required for cellular homeostasis and neurodevelopment. Yet too high concentrations of Mn and Fe in the brain are associated with toxicity and neurodegeneration, respectively. Mn can exist in multiple oxidation states, but the predominant species in the human body are Mn²⁺ and Mn³⁺. In parallel, Fe is typically present in plasma as Fe³⁺ bound to transferrin and intracellularly as Fe²⁺ in the labile iron pool and is critical for enzymatic and mitochondrial functions. Furthermore, the interaction of Mn and Fe cannot be ignored: both Mn- and Fe-specific transporters regulate export and import of manganese, ensuring proper distribution and function. Both metals support physiological brain function, yet dysregulation contributes to the development of neurological disorders. Fe depletion not only disrupts iron-dependent pathways but also enhances absorption and brain accumulation of Mn, even in the absence of excess Mn exposure. Excessive Fe accumulation in the brain is a hallmark of neurodegenerative diseases. Excessive Mn exposure can lead to manganism, a Parkinson's-like syndrome characterized by dopamine dysfunction. Previous studies have highlighted the role of Mn-Fe interactions in the etiology of neurotoxic outcomes. In this symposium, we will discuss how disturbances in Mn, Fe or their combined homeostasis can contribute to different neurological disorders such as restless leg syndrome and attention deficit hyperactivity disorder, as well as their impact in the context of environmental and occupational exposures.

• 8:30–8:50am — Manganese and iron transporters, BTBD9, and alpha-synuclein interactions in Restless LegMichael Aschner
• 8:50–9:10am — Metal constituents in air pollution and sex-dependent neurodegenerative riskMarissa Sobolewski
• 9:10–9:30am — Neuroimaging of manganese toxicity in welders with a focus on ironUlrike Dydak

Environmental and occupational exposure to metals such as uranium, cadmium, arsenic, nickel, and iron contributes to cancer risk through diverse and complex mechanisms. This symposium brings together cutting-edge research spanning molecular, cellular, and population-level studies to elucidate how metals influence carcinogenesis. Talks will explore how maternal cadmium exposure predisposes offspring to hepatocellular carcinoma and arsenic exposure's interplay with hepatic steatosis. We will examine uranium's impact on intestinal epithelial differentiation via miRNA and WNT signaling, and how PINK1 deficiency promotes mitochondrial iron accumulation and colorectal tumor growth. Additional presentations will address cadmium's disruption of lysosomal homeostasis leading to renal carcinogenesis and nickel-induced dysregulation of RNA methylation that drives malignant transformation. Collectively, these studies highlight emerging mechanisms of metal toxicity, identify biomarkers of exposure and susceptibility, and reveal therapeutic targets such as iron chelation and epigenetic modulation. By integrating mechanistic insights with translational implications, this symposium aims to advance strategies for biomonitoring, risk assessment, and intervention in metal-associated cancers.

• 10:00–10:20am — Maternal exposure to cadmium increases offspring risk for hepatocellular carcinomaLu Cai
• 10:20–10:40am — Arsenic exposure and liver diseaseHui-Chen Wu
• 10:40–11:00am — Uranium-laden particulate dust alters intestinal epithelial proliferation and differentiationJulie G In
• 11:00–11:20am — PINK1 deficiency facilitates mitochondrial iron accumulation and colon tumorigenesisXiang Xue
• 11:20–11:40am — Lysosomes as executors of cellular life-and-death decisions in cadmium carcinogenesisWing-Kee Lee
• 11:40am–12:00pm — Nickel-induced m6A dysregulation promotes malignant cell transformationHong Sun

This symposium will explore the critical role of trace metal dysregulation and environmental neurotoxicant exposure in the pathogenesis of neurodegenerative and psychiatric disorders. We will bridge clinical and translational research to highlight how imbalances in essential metals like copper and zinc, and exposure to toxicants such as lead, contribute to Alzheimer's disease (AD), mental health conditions, and related neuropathologies. The session will begin by presenting clinical evidence linking elevated systemic copper to AD and psychiatric disorders, alongside therapeutic interventions using zinc. Following this, we will delve into preclinical models demonstrating how chronic copper exposure alters the gut microbiota, accelerating AD phenotypes. The subsequent talks will uncover novel molecular mechanisms, showing how co-exposure to lead and hypertension induces astrocyte senescence via mtDNA-mediated pathways and how developmental lead exposure creates persistent neuronal vulnerabilities to AD-like pathology. Finally, we will discuss the TGF-β/PAI-1 signaling pathway as a key mediator in lead-induced amyloid deposition and explore the potential of novel metal-based compounds to counteract metal-induced neurotoxicity. This session will provide a multifaceted view of how environmental factors drive brain disorders, identifying new diagnostic biomarkers and therapeutic targets.

• 1:30–1:50pm — Copper imbalance and zinc intervention in neurodegeneration and mental disorders: Clinical and translational perspectivesRosanna Squitti
• 1:50–2:10pm — Impact of chronic copper exposure on the gut microbiota and accelerated development of Alzheimer's disease phenotypes in miceMasashi Kitazawa
• 2:10–2:30pm — Co-exposure to environmental lead and hypertension exacerbates astrocyte senescence via mtDNA-mediated cGAS phase separationYanshu Zhang
• 2:30–2:50pm — Persistent vulnerabilities in neurons following lead (Pb) exposure and implications for Alzheimer's DiseaseChongli Yuan
• 2:50–3:10pm — Endothelial PAI-1 drives lead-induced cerebral amyloid angiopathy via activation of C3⁺ Decorin⁺ A1-like astrocytesYansheng Du
• 3:10–3:30pm — A novel copper chelator reverses neuropathology and improves cognition in an Alzheimer's Disease modelGiselle Cerchiaro

Environmental metal exposures represent a persistent risk to nervous system health, yet the neuronal pathways and mechanisms disrupted by distinct metals remain incompletely defined. This symposium brings together integrative studies across multiple species and models to unravel how lead (Pb), hexavalent chromium [Cr(VI)], manganese (Mn), and iron (Fe) uniquely target and impair neuronal systems. Developmental Pb exposure disrupts multiple levels of glutamatergic neurotransmission, altering glutamate synthesis, storage, and release, while inducing lipidomic changes that converge on cognitive dysfunction. Cr(VI) exposure reveals selective vulnerability of GABAergic neurons, progressing to broader degeneration of cholinergic and dopaminergic neurons with prolonged exposure, leading to marked behavioral alterations. Mn accumulation within the basal ganglia induces motor disease, and neuron-specific modulation of Mn levels identifies dopaminergic and glutamatergic neurons as primary sites of toxicity. Finally, inhaled Fe-oxide nanoparticles derived from air pollution produce sex-specific cognitive and motor deficits, alongside structural and molecular hallmarks similar to neurodegenerative pathology. By spanning molecular, cellular, and behavioral outcomes across models, this trainee-led proposal highlights convergent and divergent pathways of metal-induced neurotoxicity. The collective insights emphasize glutamatergic, GABAergic, dopaminergic, and apoptotic mechanisms as key targets through which metals compromise neuronal function and increase risk for neurodegenerative disease.

• 3:30–3:50pm — Disruption of glutamatergic neurotransmission by developmental lead exposure drives cognitive impairments in zebrafish larvaeWagner Tamagno
• 3:50–4:10pm — Hexavalent chromium preferentially targets GABAergic neurons in a Caenorhabditis elegans model: Assessing neuronal morphologies and altered behaviorsSamuel Vielee
• 4:10–4:30pm — In-vivo repressor screen identifies dopaminergic and glutamatergic neurons as targets of manganese toxicityAshvini Melkote
• 4:30–4:50pm — Air-pollution derived Fe-oxide nanoparticle inhalation and neurodegenerative riskJithin V. George

We have understood that metals such as lead, cadmium, selenium, mercury, manganese and uranium pose human health risks for centuries. Various metals have been shown to have substantial impact on neurological, cardiovascular, and reproductive health. Given frequent use in society, we can find these metals ubiquitously throughout our environment. However, some communities face disproportionate exposure to and health impacts from these metals. Some of these areas have been termed 'sacrifice zones' for the way that environmental burdens increase over time. Meanwhile, many of these communities simultaneously face additional challenges such as poverty, and limited access to resources which can complicate the situation. These combined challenges can make finding solutions, understanding the scope of health impacts, or even simply the extent of exposure challenging. This symposium will focus on research which highlights communities around the globe which are facing these challenges. Together, this work highlights the need to continue research which evaluates exposure and health impacts of metals within impacted communities.

• 5:30–5:50pm — Longitudinal association metal exposure and mild cognitive impairment in ItaliansTommaso Filippini
• 5:50–6:10pm — Health effects of high selenium exposure through drinking water in ItalyMarco Vinceti
• 6:10–6:30pm — Metal exposure in northwestern Indiana, USAEllen Wells
• 6:30–6:50pm — Multi-metal concentrations in bone among residents of Fallujah, IraqAaron Specht
• 6:50–7:10pm — Lead exposure and health risks in riparian communities of the Amazon: linking diet, environment, and vulnerabilityFernando Barbosa, Jr.

We present a proposal for a symposium that focuses on the latest research on manganese (Mn)-induced neurotoxicity, which is a major public health problem worldwide. The last decade has seen a revolution in understanding of Mn-induced disease and control of Mn homeostasis because of: (1) the discoveries of three hereditary disorders of Mn metabolism; (2) increasing understanding of human effects of Mn exposure from epidemiology studies; (3) results of multi-omics studies providing understandings of mechanisms of Mn-induced neurotoxicity; and (4) description of the first mammalian control mechanism that protects against Mn toxicity. This proposal builds on a successful session on Mn homeostasis and neurotoxicity in ISTERH 2022 and 2024 to bring together the leading experts in the field to present their recent and on-going molecular, rodent, and worm work on the topic. Due to the timeliness, the symposium will be of wide interest to neurotoxicologists, metal biologists, geneticists, epidemiologists, and clinicians.

• 8:30–8:50am — Role of SLC30A10 in modulating Mn homeostasis and neurotoxicitySomshuvra Mukhopadhyay
• 8:50–9:10am — Congruence of human and animal model findings shows that developmental manganese exposure causes lasting neurodevelopmental deficits accompanied with pre-frontal cortex dysfunctionDonald R. Smith
• 9:10–9:30am — Polyglutamine aggregation in the Caenorhabditis elegans model of Huntington's disease alters manganese homeostasisDaiana Silva de Ávila
• 9:30–9:50am — Developmental pathophysiology of childhood-onset manganese-induced dystonia-Parkinsonism in Slc39a14-KO miceTomás R. Guilarte

• 10:30–10:50am — Introduction to blood-brain interfaces and the impact of developmental insults on brain barrier functionsJean-Francois Ghersi-Egea
• 10:50–11:10am — sox9a and sox9b as critical regulators of dioxin-induced neurovascular toxicityJess Plavicki
• 11:10–11:30am — Detrimental effects of hypoxemia on the brain barriers: A possible role in fine particulate matter-induced damage to the brainZoran Redzic
• 11:30–11:50am — Lead and selenium in amyotrophic lateral sclerosis (ALS): Evidence from human cerebrospinal fluid studiesPer M Roos
• 11:50am–12:10pm — Choroid plexus mitochondrial dysfunction as a driver of suppressed CSF production and clearance failure with trace-metal imbalance in neurodegenerationPer Selnes
• 12:10–12:30pm — Novel concept of choroid Epithelia-Ventricle Interactive Lineage (EVIL) axis in Brain: Implication in metal-induce neurotoxicitiesWei Zheng