Sleep matters: Neurodegeneration spectrum heterogeneity, combustion and friction ultrafine particles, industrial nanoparticle pollution, and sleep disorders-Denial is not an option.

Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aß1 - 42), α-synuclein (α syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority.

Alzheimer and Parkinson diseases, frontotemporal lobar degeneration and amyotrophic lateral sclerosis overlapping neuropathology start in the first two decades of life in pollution exposed urbanites and brain ultrafine particulate matter and industrial nanoparticles, including Fe, Ti, Al, V, Ni, Hg, Co, Cu, Zn, Ag, Pt, Ce, La, Pr and W are key players. Metropolitan Mexico City health crisis is in progress.

The neuropathological hallmarks of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS) are present in urban children exposed to fine particulate matter (PM2.5), combustion and friction ultrafine PM (UFPM), and industrial nanoparticles (NPs). Metropolitan Mexico City (MMC) forensic autopsies strongly suggest that anthropogenic UFPM and industrial NPs reach the brain through the nasal/olfactory, lung, gastrointestinal tract, skin, and placental barriers. Diesel-heavy unregulated vehicles are a key UFPM source for 21.8 million MMC residents. We found that hyperphosphorylated tau, beta amyloid1-42, α-synuclein, and TAR DNA-binding protein-43 were associated with NPs in 186 forensic autopsies (mean age 27.45 ± 11.89 years). The neurovascular unit is an early NPs anatomical target, and the first two decades of life are critical: 100% of 57 children aged 14.8 ± 5.2 years had AD pathology; 25 (43.9%) AD+TDP-43; 11 (19.3%) AD + PD + TDP-43; and 2 (3.56%) AD +PD. Fe, Ti, Hg, Ni, Co, Cu, Zn, Cd, Al, Mg, Ag, Ce, La, Pr, W, Ca, Cl, K, Si, S, Na, and C NPs are seen in frontal and temporal lobes, olfactory bulb, caudate, substantia nigra, locus coeruleus, medulla, cerebellum, and/or motor cortical and spinal regions. Endothelial, neuronal, and glial damages are extensive, with NPs in mitochondria, rough endoplasmic reticulum, the Golgi apparatus, and lysosomes. Autophagy, cell and nuclear membrane damage, disruption of nuclear pores and heterochromatin, and cell death are present. Metals associated with abrasion and deterioration of automobile catalysts and electronic waste and rare earth elements, i.e., lanthanum, cerium, and praseodymium, are entering young brains. Exposure to environmental UFPM and industrial NPs in the first two decades of life are prime candidates for initiating the early stages of fatal neurodegenerative diseases. MMC children and young adults-surrogates for children in polluted areas around the world-exhibit early AD, PD, FTLD, and ALS neuropathological hallmarks forecasting serious health, social, economic, academic, and judicial societal detrimental impact. Neurodegeneration prevention should be a public health priority as the problem of human exposure to particle pollution is solvable. We are knowledgeable of the main emission sources and the technological options to control them. What are we waiting for?

Environmentally Toxic Solid Nanoparticles in Noradrenergic and Dopaminergic Nuclei and Cerebellum of Metropolitan Mexico City Children and Young Adults with Neural Quadruple Misfolded Protein Pathologies and High Exposures to Nano Particulate Matter.

Quadruple aberrant hyperphosphorylated tau, beta-amyloid, α-synuclein and TDP-43 neuropathology and metal solid nanoparticles (NPs) are documented in the brains of children and young adults exposed to Metropolitan Mexico City (MMC) pollution. We investigated environmental NPs reaching noradrenergic and dopaminergic nuclei and the cerebellum and their associated ultrastructural alterations. Here, we identify NPs in the locus coeruleus (LC), substantia nigrae (SN) and cerebellum by transmission electron microscopy (TEM) and energy-dispersive X-ray spectrometry (EDX) in 197 samples from 179 MMC residents, aged 25.9 ± 9.2 years and seven older adults aged 63 ± 14.5 years. Fe, Ti, Hg, W, Al and Zn spherical and acicular NPs were identified in the SN, LC and cerebellar neural and vascular mitochondria, endoplasmic reticulum, Golgi, neuromelanin, heterochromatin and nuclear pore complexes (NPCs) along with early and progressive neurovascular damage and cerebellar endothelial erythrophagocytosis. Strikingly, FeNPs 4 ± 1 nm and Hg NPs 8 ± 2 nm were seen predominantly in the LC and SN. Nanoparticles could serve as a common denominator for misfolded proteins and could play a role in altering and obstructing NPCs. The NPs/carbon monoxide correlation is potentially useful for evaluating early neurodegeneration risk in urbanites. Early life NP exposures pose high risk to brains for development of lethal neurologic outcomes. NP emissions sources ought to be clearly recognized, regulated, and monitored; future generations are at stake.

Environmental Nanoparticles Reach Human Fetal Brains.

Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8-15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8-15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences.

Environmental Fe, Ti, Al, Cu, Hg, Bi, and Si Nanoparticles in the Atrioventricular Conduction Axis and the Associated Ultrastructural Damage in Young Urbanites: Cardiac Arrhythmias Caused by Anthropogenic, Industrial, E-Waste, and Indoor Nanoparticles.

Air pollution exposure is a risk factor for arrhythmia. The atrioventricular (AV) conduction axis is key for the passage of electrical signals to ventricles. We investigated whether environmental nanoparticles (NPs) reach the AV axis and whether they are associated with ultrastructural cell damage. Here, we demonstrate the detection of the shape, size, and composition of NPs by transmission electron microscopy (TEM) and energy-dispersive X-ray spectrometry (EDX) in 10 subjects from Metropolitan Mexico City (MMC) with a mean age of 25.3 ± 5.9 and a 71-year-old subject without cardiac pathology. We found that in every case, Fe, Ti, Al, Hg, Cu, Bi, and/or Si spherical or acicular NPs with a mean size of 36 ± 17 nm were present in the AV axis in situ, freely and as conglomerates, within the mitochondria, sarcomeres, lysosomes, lipofuscin, and/or intercalated disks and gap junctions of Purkinje and transitional cells, telocytes, macrophages, endothelium, and adjacent atrial and ventricular fibers. Erythrocytes were found to transfer NPs to the endothelium. Purkinje fibers with increased lysosomal activity and totally disordered myofilaments and fragmented Z-disks exhibited NP conglomerates in association with gap junctions and intercalated disks. AV conduction axis pathology caused by environmental NPs is a plausible and modifiable risk factor for understanding common arrhythmias and reentrant tachycardia. Anthropogenic, industrial, e-waste, and indoor NPs reach pacemaker regions, thereby increasing potential mechanisms that disrupt the electrical impulse pathways of the heart. The cardiotoxic, oxidative, and abnormal electric performance effects of NPs in pacemaker locations warrant extensive research. Cardiac arrhythmias associated with nanoparticle effects could be preventable.

Understanding the ion-induced elongation of silver nanoparticles embedded in silica.

In this work we have studied the elongation of silver nanoparticles irradiated with 40 MeV Bromine ions by means of in situ optical measurements, transmission electron microscopy and molecular dynamics simulations. The localized surface plasmon resonance of silver nanoparticles has a strong dependence on the particle shape and size, which allowed us to obtain the geometrical parameters with remarkable accuracy by means of a fit of the optical spectra. Optical results have been compared with transmission electron microscopy images and molecular dynamics simulations and the agreement is excellent in both cases. An important advantage of in situ measurements is that they yield an extremely detailed information of the full elongation kinetics. Final nanoparticle elongation depends on a complex competition between single-ion deformation, Ostwald ripening and dissolution. Building and validating theoretical models with the data reported in this work should be easier than with the information previously available, due to the unprecedented level of kinetic details obtained from the in situ measurements.