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.
Highlights
Increasing evidence links air pollution (AP) exposure to effects on the central nervous system structure and function
AP appears to be associated with amyotrophic lateral sclerosis (ALS), a disease damaging the neurons of the brain and spinal cord, leading to progressive muscle weakness [68,69,70]
This paper examines that premise based upon inhalation exposure studies; some studies using intranasal instillation are included, but it is important to note that non-physiological bolus-type instillation exposures are significantly different in terms of the exorbitant dose and dose rate, as well as, importantly, deposition throughout the respiratory tract
Summary
One source of such neurotoxicity could be the metals and trace element contaminants of particulate matter [83], which include both metals essential to brain as well as non-essential elements. The metals and trace elements identified in PM arise from numerous anthropogenic sources, including mechanical engine wear, emissions from tail pipes, brake wear, coal-fired power plants, oil combustion processes, metal refineries, metal ore smelting and processing, and other industries [83] Most such metals/elements, including those from roadway traffic, are insoluble, but can be solubilized and subsequently lead to redox cycling and oxidative stress in vivo. Studies from our laboratory in mice demonstrate the potential for inhaled ambient AP to alter in vivo both the profile and level of metals in the brain [92]. Alterations in thealterations levels of metals focus studies on NDDs on peripheral markers rather than the brain. Alterations the brain metal levels have beenlevels reported [109,110], have correlations of trace geographic in location. Alterations in mitochondrial Ca homeostasis are considered to contribute to neuronal loss in PD [149], and has been postulated to serve as a key mechanism in the etiology of AD [150] and ALS [151]
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