Numerous epidemiological and experimental studies have shown that air pollution is harmful to health and that exposure to particulate matter (PM) is mainly associated with diseases of the cardiovascular and respiratory systems. However, a growing body of evidence suggests that the nervous system is also a target, mainly by particulate compounds in the smallest particle size fractions (UFPs), mainly derived from urban traffic emissions. Responsible for several neurodegenerative diseases, the damaging effects of air pollution are believed to stem from elevated inflammation and oxidative stress. A central part of the olfactory epithelium, a key site of entry of air pollutants into the brain, the olfactory mucosa, located at the roof of the nasal cavity and directly exposed to the external environment, allows olfactory receptors to detect suspended particles in the ambient air and to transmit, via the olfactory nerve, information directly to the brain, without having to cross the protective barriers of the central nervous system. The highly plastic olfactory system consequently offers important advantages for research, including an easily accessible olfactory mucosa with multipotent adult neural stem cells, applications for studying the entry of airborne pollutants and infectious agents into the body and for studying the relationship between environmental factors and neurodegeneration. A group of disorders characterised by the progressive death of neurons resulting in the deterioration of central and/or peripheral nervous system function, to date, despite numerous clinical studies and years of research, there is no cure for neurodegenerative diseases. Post-mortem brain tissue is valuable for understanding neurodegeneration, but is often of poor quality and availability. Studies on live animal models help to explore the disease, but differences between species limit their applicability to humans. In vitro models created by patients offer an alternative, allowing for the identification of patient-specific changes and possible biomarkers. Growing evidence of olfactory mucosal dysfunction as an early marker of neuropathogenesis has paved the way for an in-depth investigation of its role in how the brain copes with environmental exposures, and although the exact ways in which it responds to air pollutants have yet to be fully elucidated, previous work with a primary human cell culture model of olfactory mucosa has revealed mitochondrial dysfunction, inflammation and apoptotic features following exposure of cultures to particulate matter collected from an urban environment. The aim of the study conducted by researchers from the cellular neurobiology group of the A.I. Virtanen Institute for Molecular Sciences in Eastern Finland, published in the journal Science of The Total Environment,Volume 905, 2023, 'Emissions from modern engines induce distinct effects in human olfactory mucosa cells, depending on fuel and after treatment', was to provide new insights into the impact of exhaust emissions on the human olfactory mucosa by comparing the effects of exposure to different fuels and engine technologies, with a particular focus on the effects of the UFPs fraction of emissions. The results showed that exhaust from engines with state-of-the-art filtration and after-treatment were less harmful to olfactory mucosa cells than modern engines without filters: Euro6 exhaust caused negligible changes, demonstrating the importance of after-treatment devices on the adverse effects observed in human-derived olfactory mucosa cells in vitro. In contrast, exposure to A0 and A20 caused substantial alterations in the gene expression profile and function of olfactory mucosa.
Numerosi di studi epidemiologici e sperimentali hanno dimostrato che l’inquinamento atmosferico è dannoso per la salute e che l’esposizione al particolato (PM) è principalmente associata a malattie del sistema cardiovascolare e respiratorio. Tuttavia, un numero crescente di evidenze suggerisce che anche il sistema nervoso ne è un bersaglio, soprattutto ad opera dei composti di particolato nelle frazioni dimensionali più piccole (UFPs), derivate principalmente dalle emissioni del traffico urbano. Responsabile di diverse malattie neurodegenerative, si ritiene che gli effetti dannosi dell’inquinamento atmosferico derivino da un’elevata infiammazione e dallo stress ossidativo. Parte centrale dell’epitelio olfattivo, sito chiave di ingresso degli inquinanti atmosferici nel cervello, la mucosa olfattiva, situata sul tetto della cavità nasale e direttamente esposta all’ambiente esterno, permette ai recettori olfattivi di rilevare le particelle sospese presenti nell’aria ambiente e di trasmettere, attraverso il nervo olfattivo, le informazioni direttamente al cervello, senza dover attraversare le barriere protettive del sistema nervoso centrale. Il sistema olfattivo, altamente plastico, offre di conseguenza importanti vantaggi per la ricerca, tra i quali una mucosa olfattiva facilmente accessibile, con cellule staminali neurali adulte multipotenti, applicazioni per lo studio dell’ingresso nell’organismo di agenti inquinanti e infettivi presenti nell’aria e per lo studio della relazione tra fattori ambientali e neurodegenerazione. Gruppo di disturbi caratterizzati dalla progressiva morte dei neuroni che genera nel deterioramento delle funzioni del sistema nervoso centrale e/o periferico, ad oggi, nonostante i numerosi studi clinici e gli anni di ricerca, non esistono cure per le malattie neurodegenerative. Il tessuto cerebrale post-mortem è prezioso per comprendere la neurodegenerazione, ma spesso è di scarsa qualità e disponibilità. Gli studi su modelli animali vivi aiutano a esplorare la malattia, ma le differenze tra specie limitano la loro applicabilità all'uomo. I modelli in vitro creati dai pazienti offrono un'alternativa, consentendo di identificare cambiamenti specifici nel paziente e possibili biomarcatori. La crescente evidenza della disfunzione della mucosa olfattiva come marcatore precoce della neuropatogenesi ha aperto la strada a un’indagine approfondita del ruolo che riveste nel modo in cui il cervello affronta le esposizioni ambientali e, nonostante le modalità esatte con cui risponde agli inquinanti atmosferici non siano ancora state del tutto chiarite, precedenti lavori con un modello di coltura cellulare umano primario di mucosa olfattiva hanno rivelato disfunzione mitocondriale, infiammazione e caratteristiche apoptotiche a seguito dell’esposizione delle colture a particolato raccolto da un ambiente urbano. Scopo dello studio condotto dai ricercatori del gruppo di neurobiologia cellulare dell’A.I. Virtanen Institute for Molecular Sciences della Finlandia Orientale, pubblicato sulla rivista Science of The Total Environment,Volume 905, 2023, “Emissions from modern engines induce distinct effects in human olfactory mucosa cells, depending on fuel and after treatment”, è stato quello di fornire nuove conoscenze sull’impatto delle emissioni di gas di scarico sulla mucosa olfattiva umana, confrontando gli effetti dell’esposizione a diversi carburanti e tecnologie motoristiche, con particolare focus agli effetti della frazione UFPs delle emissioni. I risultati hanno dimostrato che lo scarico dei motori con filtrazione e post-trattamento all’avanguardia sono meno dannosi per le cellule.
Mucosa olfattiva umana: modelli in vitro per indagare sugli effetti dell'esposizione agli inquinanti atmosferici
NASSER, HOUSSEIN
2022/2023
Abstract
Numerous epidemiological and experimental studies have shown that air pollution is harmful to health and that exposure to particulate matter (PM) is mainly associated with diseases of the cardiovascular and respiratory systems. However, a growing body of evidence suggests that the nervous system is also a target, mainly by particulate compounds in the smallest particle size fractions (UFPs), mainly derived from urban traffic emissions. Responsible for several neurodegenerative diseases, the damaging effects of air pollution are believed to stem from elevated inflammation and oxidative stress. A central part of the olfactory epithelium, a key site of entry of air pollutants into the brain, the olfactory mucosa, located at the roof of the nasal cavity and directly exposed to the external environment, allows olfactory receptors to detect suspended particles in the ambient air and to transmit, via the olfactory nerve, information directly to the brain, without having to cross the protective barriers of the central nervous system. The highly plastic olfactory system consequently offers important advantages for research, including an easily accessible olfactory mucosa with multipotent adult neural stem cells, applications for studying the entry of airborne pollutants and infectious agents into the body and for studying the relationship between environmental factors and neurodegeneration. A group of disorders characterised by the progressive death of neurons resulting in the deterioration of central and/or peripheral nervous system function, to date, despite numerous clinical studies and years of research, there is no cure for neurodegenerative diseases. Post-mortem brain tissue is valuable for understanding neurodegeneration, but is often of poor quality and availability. Studies on live animal models help to explore the disease, but differences between species limit their applicability to humans. In vitro models created by patients offer an alternative, allowing for the identification of patient-specific changes and possible biomarkers. Growing evidence of olfactory mucosal dysfunction as an early marker of neuropathogenesis has paved the way for an in-depth investigation of its role in how the brain copes with environmental exposures, and although the exact ways in which it responds to air pollutants have yet to be fully elucidated, previous work with a primary human cell culture model of olfactory mucosa has revealed mitochondrial dysfunction, inflammation and apoptotic features following exposure of cultures to particulate matter collected from an urban environment. The aim of the study conducted by researchers from the cellular neurobiology group of the A.I. Virtanen Institute for Molecular Sciences in Eastern Finland, published in the journal Science of The Total Environment,Volume 905, 2023, 'Emissions from modern engines induce distinct effects in human olfactory mucosa cells, depending on fuel and after treatment', was to provide new insights into the impact of exhaust emissions on the human olfactory mucosa by comparing the effects of exposure to different fuels and engine technologies, with a particular focus on the effects of the UFPs fraction of emissions. The results showed that exhaust from engines with state-of-the-art filtration and after-treatment were less harmful to olfactory mucosa cells than modern engines without filters: Euro6 exhaust caused negligible changes, demonstrating the importance of after-treatment devices on the adverse effects observed in human-derived olfactory mucosa cells in vitro. In contrast, exposure to A0 and A20 caused substantial alterations in the gene expression profile and function of olfactory mucosa.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/16980