Particulate Air Pollution and Risk of Neuropsychiatric Outcomes. What We Breathe, Swallow, and Put on Our Skin Matters

Abstract

We appraise newly accumulated evidence of the impact of particle pollution on the brain, the portals of entry, the neural damage mechanisms, and ultimately the neurological and psychiatric outcomes statistically associated with exposures. PM pollution comes from natural and anthropogenic sources such as fossil fuel combustion, engineered nanoparticles (NP ≤ 100 nm), wildfires, and wood burning. We are all constantly exposed during normal daily activities to some level of particle pollution of various sizes-PM_2.5 (≤2.5 µm), ultrafine PM (UFP ≤ 100 nm), or NPs. Inhalation, ingestion, and dermal absorption are key portals of entry. Selected literature provides context for the US Environmental Protection Agency (US EPA) ambient air quality standards, the conclusions of an Independent Particulate Matter Review Panel, the importance of internal combustion emissions, and evidence suggesting UFPs/NPs cross biological barriers and reach the brain. NPs produce oxidative stress and neuroinflammation, neurovascular unit, mitochondrial, endoplasmic reticulum and DNA damage, protein aggregation and misfolding, and other effects. Exposure to ambient PM_2.5 concentrations at or below current US standards can increase the risk for TIAs, ischemic and hemorrhagic stroke, cognitive deficits, dementia, and Alzheimer's and Parkinson's diseases. Residing in a highly polluted megacity is associated with Alzheimer neuropathology hallmarks in 99.5% of residents between 11 months and ≤40 y. PD risk and aggravation are linked to air pollution and exposure to diesel exhaust increases ALS risk. Overall, the literature supports that particle pollution contributes to targeted neurological and psychiatric outcomes and highlights the complexity of the pathophysiologic mechanisms and the marked differences in pollution profiles inducing neural damage. Factors such as emission source intensity, genetics, nutrition, comorbidities, and others also play a role. PM_2.5 is a threat for neurological and psychiatric diseases. Thus, future research should address specifically the potential role of UFPs/NPs in inducing neural damage.

Keywords: Alzheimer’s; Parkinson’s; air pollution; internal combustion emissions; nanoparticles; particulate matter; pollution neurology and psychiatric outcomes; quadruple aberrant proteins; ultrafine particles; wildfires.

Figure 1

Black carbon particulates from wildfires spreads eastward across the U.S. 21 July 2021 (Image credit: Joshua Stevens/NASA Earth Observatory) Accessed on 24 July 2021.

Figure 2

Electron micrographs of neurovascular unit (NVU) and neural organelles in Metropolitan Mexico City children. (A) Three-year-old boy, substantia nigrae pars compacta showing a capillary with one luminal red blood cell (RBC) surrounded by an extensively vacuolated, fragmented neuropil (*). (B) Cerebellar granular neurons from same child as (A), showing nanoparticles (arrowheads) in intranuclear location and at the membrane interphase between neurons (short arrow). (C) Fifteen-year-old substantia nigrae pars compacta showing numerous mitochondria (M) with abnormal cristae and neuromelanin structures (NM) with nanoparticles. (D) In a closeup, the mitochondria exhibit numerous nanoparticles in the matrix, cristae, and along the double layer mitochondrial wall (arrows).

Figure 3

Light microscopy, immunohistochemistry (IHC) of aberrant neural proteins in MMC children and young adults. (A) Frontal cortex in an 11-month-old APOE 3/3 showing an Aβ diffuse plaque. IHC Aβ 17–24, 4G8, Covance, Emeryville, CA 1:1500, DAB brown product. (B) Temporal cortex, 11 y old child APOE 3/3 with multiple trans-cortical diffuse and mature Aβ plaques, 4G8 brown product. (C) Adult 36 y old, APOE 3/4, temporal cortex with mature amyloid plaques (arrowheads) and reactive astrocytes (short arrow). Double staining 4G8 red product, and glial acidic fibrillary protein (GAFP) brown product. (D) Two-year-old frontal cortex with granular cytoplasmic staining for hyperphosphorylated tau (P-tau) (short arrows). PHF-tau 8 phosphorylated at Ser 199–202-Thr 205, Innogenetics, Belgium, AT-8 1:1000, brown DAB product. (E) Eleven-year-old frontal cortex with pyramidal neuron granular cytoplasmic immunoreactivity for P-tau. (F) Forty-year-old male with numerous tangles supra and infratentorial, including substantia nigrae (short arrow), P-tau neurite (long arrow), and granular cytoplasmic immunoreactivity (arrowheads). AT-8 brown product. (G) Same 11 y old child as (E) with TPD-43 immunoreactivity in brainstem neurons, the nuclei (n) are negative, and the cytoplasm exhibits granular immunoreactivity (short arrows). TDP-43 red product. (H) Thirty-five-year old male, cochlear nuclei neurons positive for α-synuclein, phosphorylated at Ser-129, LB509, In Vitrogen, Carlsbad CA 1:1000. Red product counterstained with hematoxylin.