Combustion-derived nanoparticles, the neuroenteric system, cervical vagus, hyperphosphorylated alpha synuclein and tau in young Mexico City residents

• Published in: Environmental research 2017-11, Vol.159, p.186-201
• Main Authors: Calderón-Garcidueñas, Lilian, Reynoso-Robles, Rafael, Pérez-Guillé, Beatriz, Mukherjee, Partha S., Gónzalez-Maciel, Angélica
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Air Pollutants - toxicity; Alpha synuclein; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Alzheimer; Animals; Biomarkers - analysis; Child; Children; Cities; Combustion-derived nanoparticles; Dogs; Female; GI barrier; Humans; Hyperphosphorylated tau; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Intestinal Mucosa - ultrastructure; Intestine, Small - drug effects; Intestine, Small - pathology; Intestine, Small - ultrastructure; Male; Mexico; Mexico City; Microscopy, Electron, Transmission; Nanoparticles - toxicity; Neuroenteric system; Parkinson; Phosphorylation; RNA, Messenger - analysis; tau Proteins - genetics; tau Proteins - metabolism; Tight Junctions - drug effects; Tight Junctions - pathology; Tight Junctions - ultrastructure; Vagus; Vagus Nerve - drug effects; Vagus Nerve - metabolism; Vagus Nerve - ultrastructure; Vehicle Emissions - toxicity; Young Adult
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2017.08.008

Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM2.5), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls. Electron microscopy of epithelial, endothelial and neural cells and immunoreactivity of stomach and vagus to phosphorylated ɑ-synuclein Ser129 and Hyperphosphorylated-Tau (Htau) were evaluated and CDNPs measured in ENS. CDNPs were abundant in erythrocytes, unmyelinated submucosal, perivascular and intramuscular nerve fibers, ganglionic neurons and vagus nerves and associated with organelle pathology. ɑSyn and Htau were present in 25/27 MC gastric,15/26 vagus and 18/27 gastric and 2/26 vagus samples respectively. We strongly suggest CDNPs are penetrating and damaging the GI barrier and reaching preganglionic parasympathetic fibers and the vagus nerve. This work highlights the potential role of CDNPs in the neuroenteric hyperphosphorylated ɑ-Syn and tau pathology as seen in Parkinson and Alzheimer's diseases. Highly oxidative, ubiquitous CDNPs constitute a biologically plausible path into Parkinson's and Alzheimer's pathogenesis. •Swallowed CDNPs have easy access to GI epithelium and submucosa.•Damaged GI barrier facilitates damage to the enteric nervous system.•Mexico City teens and young adults have the early hallmarks of PD.•CDNPs reach preganglionic parasympathetic fibers and vagus nerves.•Highly oxidative, ubiquitous CDNPs are a plausible path into PD pathogenesis.