Air Pollution-Related Brain Metal Dyshomeostasis as a Potential Risk Factor for Neurodevelopmental Disorders and Neurodegenerative Diseases

Abstract

Increasing evidence links air pollution (AP) exposure to effects on the central nervous system structure and function. Particulate matter AP, especially the ultrafine (nanoparticle) components, can carry numerous metal and trace element contaminants that can reach the brain in utero and after birth. Excess brain exposure to either essential or non-essential elements can result in brain dyshomeostasis, which has been implicated in both neurodevelopmental disorders (NDDs; autism spectrum disorder, schizophrenia, and attention deficit hyperactivity disorder) and neurodegenerative diseases (NDGDs; Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis). This review summarizes the current understanding of the extent to which the inhalational or intranasal instillation of metals reproduces in vivo the shared features of NDDs and NDGDs, including enlarged lateral ventricles, alterations in myelination, glutamatergic dysfunction, neuronal cell death, inflammation, microglial activation, oxidative stress, mitochondrial dysfunction, altered social behaviors, cognitive dysfunction, and impulsivity. Although evidence is limited to date, neuronal cell death, oxidative stress, and mitochondrial dysfunction are reproduced by numerous metals. Understanding the specific contribution of metals/trace elements to this neurotoxicity can guide the development of more realistic animal exposure models of human AP exposure and consequently lead to a more meaningful approach to mechanistic studies, potential intervention strategies, and regulatory requirements.

The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice

“…Such an understanding can guide the development of more realistic focused animal exposure models of human AP exposure as well as allow refinement of epidemiological studies, and, consequently, a more meaningful approach to mechanistic studies. In addition, it would be potentially informative in population studies, for example, using geographic mapping of exposures to various metal contaminants of AP, along with gases such as SO 2 , where available, in relation to diagnostic or incidence data for various neurodevelopmental disorders and neurodegenerative diseases [ 30 ]. Such studies would also point to potential intervention strategies for neurodevelopmental disorders and neurodegenerative diseases.…”

“…Analyses of filters from exposure chambers in our studies revealed the presence of multiple metals and trace elements in the AP exposures that could lead to brain metal dyshomeostasis [ 30 ]. Iron (Fe) is the metal of greatest abundance in the atmosphere [ 31 ] and thus is often a dominant component of the trace element levels of particulate matter, with concentrations clearly differing by geographical and industrial source.…”

“…Correspondingly, ICP-MS analyses of brain sections from male mice exposed postnatally to concentrated ambient ultrafine particles revealed brain metal dyshomeostasis, characterized by marked elevations of metals and trace elements in brain, including Fe and sulfur (S), but that also included increases in calcium (Ca), copper (Cu) and aluminum (Al) [ 30 ]. Increases in brain Fe were also found in response to gestational exposures, particularly in female offspring [ 19 ].…”

The Role of Fossil Fuel Combustion Metals in PM2.5 Air Pollution Health Associations

“…After intratracheal instillation of mice with coal and coal fly-ash, Cr, Fe and Ni were detected in liver, spleen and brain [156] PM and associated metals have been linked to neurotoxicity and mental health [157]. Excess brain exposure to either essential or non-essential elements can result in brain dyshomeostasis, which has been implicated in both neurodevelopmental disorders (NDDs; autism spectrum disorder, schizophrenia, and attention deficit hyperactivity disorder) and neurodegenerative diseases [158]. After prenatal exposure of mice to concentrated ambient particles via inhalation, Fe, Al, and Si were metabolically distributed to the CNS [159].…”

Computational Design of Rasagiline Derivatives: Searching for Enhanced Antioxidant Capability

“…Although numerous investigations have been devoted to the elucidation of the ND pathologies, their primary causes continue elusive. Some interrelated crucial aspects on the progression of these disorders are proteopathy [6][7][8] , metal ion dyshomeostasis , environmental pollutants, [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] and neurotransmitter deficiencies. A chemical phenomenom shared by all these diseases is oxidative stress (OS).…”