The impact of environmental metals in young urbanites’ brains
Introduction
Air pollution is a complex mixture of particulate matter (PM), gases, organic and inorganic compounds present in outdoor and indoor air. Children living in Mexico City (MC) exhibit evidence of chronic inflammation of the upper and lower respiratory tracts, accumulation of ultrafine PM in nasal respiratory epithelium, breakdown of the nasal respiratory epithelial barrier, systemic inflammation, immunodysregulation, brain inflammation, cognitive and olfaction deficits, and brain magnetic resonance imaging (MRI) structural abnormalities (Calderón-Garcidueñas et al., 2001a, Calderón-Garcidueñas et al., 2001b, Calderón-Garcidueñas et al., 2003a, Calderón-Garcidueñas et al., 2003b, Calderón-Garcidueñas et al., 2004, Calderón-Garcidueñas et al., 2007, Calderón-Garcidueñas et al., 2008a, Calderón-Garcidueñas et al., 2008b, Calderón-Garcidueñas et al., 2008c, Calderón-Garcidueñas et al., 2009, Calderón-Garcidueñas et al., 2010, Calderón-Garcidueñas et al., 2011a, Calderón-Garcidueñas et al., 2011c, Block and Calderón-Garcidueñas, 2009). Children and adults exhibit up-regulation of inflammation-associated genes including cyclooxygenase-2 (COX2), interleukin 1 beta (IL-1β), and the key innate immunity receptor CD14 in their olfactory bulbs, frontal cortex, substantia nigra and vagus nerve (Calderón-Garcidueñas et al., 2004, Calderón-Garcidueñas et al., 2008b). The frontal cortex of 40% of children and young adults age 18.37 ± 6.9 years resident in Mexico City exhibited tau hyperphosphorylation with pre-tangle material and 51% had Aβ diffuse plaques compared with 0% in controls (21.8 ± 10.8 years) (Calderón-Garcidueñas et al., 2011b). Data from the same cohorts showed a significant up-regulation of gene network clusters including IL1, NF-κ B, TNF, IFN and TLRs, along with a 15 fold frontal down-regulation of the cellular prion protein (PrPC) in MC subjects (Calderón-Garcidueñas et al., 2011b). Our findings suggest that chronic exposure to severe urban air pollution causes a significant imbalance in genes essential for cell proliferation, apoptosis, oxidative stress, inflammation, innate and adaptive immune responses and early Alzheimer's disease-related pathological processes leading to neurofibrillary tangle formation start early in childhood or in early young adulthood. Moreover, clinically healthy Mexico City children performed more poorly across a variety of cognitive tests and had significant differences in white matter volumes compared to children from low polluted areas (Calderón-Garcidueñas et al., 2011c). Thus, exposures to urban pollution also perturb the trajectory of cerebral development (Calderón-Garcidueñas et al., 2011c).
Air pollution in Mexico City is severe and metals are an important component of urban particulate matter (Bravo-Alvarez and Torres-Jardón, 2002, Chow et al., 2002, Molina and Molina, 2004, Molina et al., 2007, Moreno et al., 2008, Rauch et al., 2006, Moffet et al., 2008, Querol et al., 2008, Guzmán-Morales et al., 2011). There is a significant heterogeneity in particle mass, composition and toxicity in PM10 (particulate matter < 10 μm in diameter) samples collected in Mexico City (Rosas-Pérez et al., 2007). Further, the biological effects of PM10 using in vitro tests vary according to the regions within the city from where they were collected (Alfaro-Moreno et al., 2002, Alfaro-Moreno et al., 2007).
There is an extensive literature associating health effects with ambient particulate matter and its components (Sunderman, 2001, Aschner et al., 2007, Maier et al., 2008, Happo et al., 2008, Chen and Lippman, 2009, Afeseh-Ngwa et al., 2009), and studies addressing mechanisms that mediate PM metals toxicology (Ayres et al., 2008, Kodavanti et al., 2008, Nong et al., 2008, Tang et al., 2009, Frick et al., 2011). Accumulation of metal ions in the brain contributes to heightened oxidative stress and neuronal damage (Zatta et al., 2008, Bolognin et al., 2009).
The goals of the present study were as follows: First, we set out to determine, using inductively coupled plasma mass spectrometry (ICP-MS), the content of metals associated with anthropogenic activities as well as essential metals and trace minerals related to normal brain function (V, Ni, Mn, Pb, Cr, Fe, Zn, Se, Cu, Co) in frontal cortex and in the lungs from subjects residing in high- vs. low-pollution areas. A second goal was to investigate if there was an association between the metal content in the frontal cortex and the lungs and gene expression of two inflammatory genes: COX2 and IL1β that have proven to be good markers of exposure to urban air pollution (Calderón-Garcidueñas et al., 2003b, Calderón-Garcidueñas et al., 2004, Calderón-Garcidueñas et al., 2008a, Calderón-Garcidueñas et al., 2011b, Villarreal-Calderon et al., 2010). Thirdly, since the olfactory bulb (OB) is a target and a portal of entry of air pollution components (Ali et al., 2010), we explored the relationship between frontal cortex metal concentrations and OB inflammatory and DNA repair gene responses. Finally, we assessed whether age is related to frontal cortex metal accumulation. Oxidative stress, neuroinflammation, and neurodegeneration are present early in life upon exposure to polluted megacities and environmental exposure to metals could play a critical role for the induction of inflammatory and DNA repair responses in the brain.
Section snippets
Study cities and air quality data
We selected a polluted megacity and two control cities. Mexico City (MC) was the selected megacity, while Tlaxcala and Veracruz were the low polluted cities. Mexico City represents an extreme of urban growth and environmental pollution (Bravo-Alvarez and Torres-Jardón, 2002, Molina et al., 2007). The Mexico City Metropolitan Area lies in an elevated basin at an altitude of 2240 m above mean sea level and its urbanized area covers around 2000 km2. The basin is surrounded by high mountain ridges on
Air quality data
MC residents are continuously exposed year-round to air pollutant concentrations above the United States’ current National Air Ambient Quality Standards (NAAQS). High concentrations of fine particulate matter (PM2.5) are present in MC air. Fig. 1 shows the trend of 24-h PM2.5 average concentrations from 2004 to 2010 in the Mexico City Metropolitan Area according to data from the official air quality monitoring network. The upper levels typically correspond to the northern areas and the lower
Discussion
Three major findings are seen in this work, the first one is that children and adults living in a highly polluted megacity have increased frontal cortex concentrations of road-traffic, combustion and industry-associated metals including Mn, Cr and Ni when compared with residents from lower air pollution cities. The second one, is a finding we have reported before in similar Mexico City cohorts vs. controls (Calderón-Garcidueñas et al., 2004, Calderón-Garcidueñas et al., 2008b,
Acknowledgments
This work supported in part by 1KO1 NS046410-01A1, 1R21ES013293-01, 2RO1 ES010975 and ITHS UL1RR025014.
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2023, Journal of Inorganic BiochemistryCitation Excerpt :Increased cobalt levels are found in patients with orthopedic [10,14] and orthodontic [15] appliances, and the potential for toxicity in those who consume an excess of the recommended daily allowance for vitamin B12 in supplements is a significant health concern [11,13]. Cobalt-mediated oxidative stress is an underlying cause of neuroinflammation [16], degeneration of neuronal cells [17,18], increased levels of β-amyloid in Alzheimer's disease [19], epilepsy [20], cancer [13], damage to liver-, kidney-, and lung- chromatin in rats [21], and reduction in kidney and liver function in mice [22]. Cobalt can cause DNA backbone cleavage [23] and base oxidation [24], and Co2+, Fe2+, and Cu+ bind to similar sites in DNA [25–28].