Neurological susceptibility to environmental exposures: pathophysiological mechanisms in neurodegeneration and multiple chemical sensitivity

Abstract

The World Health Organization lists air pollution as one of the top five risks for developing chronic non-communicable disease, joining tobacco use, harmful use of alcohol, unhealthy diets and physical inactivity. This review focuses on how host defense mechanisms against adverse airborne exposures relate to the probable interacting and overlapping pathophysiological features of neurodegeneration and multiple chemical sensitivity. Significant long-term airborne exposures can contribute to oxidative stress, systemic inflammation, transient receptor subfamily vanilloid 1 (TRPV1) and subfamily ankyrin 1 (TRPA1) upregulation and sensitization, with impacts on olfactory and trigeminal nerve function, and eventual loss of brain mass. The potential for neurologic dysfunction, including decreased cognition, chronic pain and central sensitization related to airborne contaminants, can be magnified by genetic polymorphisms that result in less effective detoxification. Onset of neurodegenerative disorders is subtle, with early loss of brain mass and loss of sense of smell. Onset of MCS may be gradual following long-term low dose airborne exposures, or acute following a recognizable exposure. Upregulation of chemosensitive TRPV1 and TRPA1 polymodal receptors has been observed in patients with neurodegeneration, and chemically sensitive individuals with asthma, migraine and MCS. In people with chemical sensitivity, these receptors are also sensitized, which is defined as a reduction in the threshold and an increase in the magnitude of a response to noxious stimulation. There is likely damage to the olfactory system in neurodegeneration and trigeminal nerve hypersensitivity in MCS, with different effects on olfactory processing. The associations of low vitamin D levels and protein kinase activity seen in neurodegeneration have not been studied in MCS. Table 2 presents a summary of neurodegeneration and MCS, comparing 16 distinctive genetic, pathophysiological and clinical features associated with air pollution exposures. There is significant overlap, suggesting potential comorbidity. Canadian Health Measures Survey data indicates an overlap between neurodegeneration and MCS (p < 0.05) that suggests comorbidity, but the extent of increased susceptibility to the other condition is not established. Nevertheless, the pathways to the development of these conditions likely involve TRPV1 and TRPA1 receptors, and so it is hypothesized that manifestation of neurodegeneration and/or MCS and possibly why there is divergence may be influenced by polymorphisms of these receptors, among other factors.

An Untargeted Genome-Wide Snp Investigation of Chemical Intolerance

“…Those shared health effects are common among individuals diagnosed with CI. This implies that important gene/chemical exposure interactions may in uence the development or exacerbation of the health effects associated with CI (Molot et al, 2021). Up-or down-regulated disruption of the genes by these chemicals may in uence the severity of symptoms among individuals with CI.…”

Migraine and air pollution: A systematic review

“…Future multi‐pollutant modeling would increase clarity about the individual and additive impacts of the complex chemical mixtures in the air we breathe. Measurement of co‐pollutants beyond those reported here is often challenging; however, interesting work is being carried out to estimate the reactive oxygen potential of air pollution, 54 which could be applicable to migraine 4,6,9 …”

“…Air pollution is a ubiquitous exposure that impacts respiratory and cardiovascular health, 3 and has been proposed as a potential trigger for migraine 4–6 . The potential biological mechanism through which air pollution may trigger migraine attacks is not yet fully understood.…”

Mitoapocynin Attenuates Organic Dust Exposure-Induced Neuroinflammation and Sensory-Motor Deficits in a Mouse Model

“…Exposure to contaminants have been shown to be a major etiology of neurodegenerative diseases with an underlying inflammatory process (Molot et al, 2021 ). Higher prevalence of neurodegenerative disorders, such as PD and AD in people living in the Midwestern and northeastern parts of the USA, is concerning due to a possible link to persistent exposure to agriculture contaminants (Wright Willis et al, 2010 ; U.S. Geological Survey, 2021 ).…”