Air Pollution and Children: Neural and Tight Junction Antibodies and Combustion Metals, the Role of Barrier Breakdown and Brain Immunity in Neurodegeneration

Abstract

Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond

“…In the setting of urban air pollution, the evolution of a changing paradigm favoring a pathogen penetrating an epithelial lining and via transsynaptic transmission reaching preganglionic parasympathetic motor neurons of the vagus nerve [63] has to entertain environmental swallowed particulate matter as a potential culprit. We suggested that damage to epithelial and endothelial barriers associated to air pollution exposures is a robust trigger of tight junction and neural antibodies [31]. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology present in megacity children.…”

“…Continuous expression of potent inflammatory mediators in the CNS and the formation of reactive oxygen species (ROS) are major findings in urban residents. Ultrafine PM (UFPM), PM-LPS, and metal uptake take place through olfactory neurons, cranial nerves such as the trigeminal and vagus, the GI tract, the systemic circulation, and macrophage-like cells loaded with PM from the lungs [31][32][33][34][35][36].…”

“…There is evidence the GI tract barrier is also compromised in the air pollution setting and recent research links inflammatory bowel diseases, changes in gut microbiome, and abdominal pain with air pollution [59][60][61][62]. The integrity of the gastrointestinal (GI) barrier is compromised in MC dogs and could be altered in MC children as evidenced by the autoimmune response to TJ and neural proteins [31,36].…”

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…Long-term air pollution in cities relates to neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of beta-amyloid in children and young adults [290]. Air pollution also disrupts epithelial and endothelial barriers and triggers autoimmune responses involving tight junction and neural autoantibodies [291].…”

Neurological Disorders from Ambient (Urban) Air Pollution Emphasizing UFPM and PM2.5

“…In another study carried out on 50 Mexico City Metropolitan Area (MCMA) children having ages 13.4 ± 4.8 years on urban air pollution reveled decreased attention, short-term memory, and below-average levels of intelligent quotient [20]. A different study performed in the same area (MCMA), 139 children having ages 11.91 ± 4.2 year were reported [21] to show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and BBB breakdown from exposures of urban air pollution. Air pollution was shown [22] to adversely affect the cognitive-function and-performance in elderly women, in which the impact of the traffic exposure was significant to those carrying the apolipoprotein E (APOE) ε4 allele the most prevalent genetic risk for AD.…”