Descrizione del progetto
Approfondire il ruolo delle nanoplastiche nei disturbi neurologici
Le nanoparticelle di plastica, rilevate in svariati ecosistemi, possono muoversi dall’intestino al sistema linfatico e circolatorio, e attraversare la barriera ematoencefalica dei mammiferi. Tuttavia, gli effetti a lungo termine delle nanoplastiche sul cervello sono sconosciuti. Le microglia sono cellule neuroimmuni che percepiscono e rispondono ai cambiamenti ambientali. Sono fondamentali per la omeostasi neuronale e potrebbero essere attivate dalle nanoplastiche che raggiungono il cervello. Il progetto NanoGlia, finanziato dall’UE, utilizzerà modelli animali di roditori per approfondire i cambiamenti comportamentali, cellulari e molecolari nel cervello a seguito dell’ingestione di nanoplastiche. Il progetto studierà gli eventi di riprogrammazione evolutivi indotti dalle nanoplastiche nelle microglia fetali che potrebbero influenzare l’organogenesi e il funzionamento del cervello. NanoGlia cerca di comprendere il modo in cui le nanoplastiche provocano l’attivazione delle microglia durante l’embriogenesi e nelle fasi postnatali, e se quest’attivazione immunitaria possa portare a cambiamenti permanenti dello sviluppo e del funzionamento cerebrale.
Obiettivo
An omnipresent but understudied environmental risk for our immune system is pollution by nano-sized plastics. Plastic particles have been detected in a wide variety of ecosystems and are speculated to enter and spread in the food web all the way to humans. Ingested nanoplastics can translocate from the gut to the lymph and circulatory systems and have the capacity to cross the blood-brain barrier in mammals. It has been recently shown that nanoplastics cause behavioural disorders in fish, and thus may also represent a risk for human health, in particular for brain function. However, the long-term bioavailability and toxicity of nanoplastics in the brain are unknown. Microglia as the main neuroimmune cells have not only a defence function required during inflammatory conditions, but constantly sense and response to environmental changes as part of their housekeeping functions that are essential for neuronal homeostasis. This places microglia at the interface between normal and abnormal brain development and function. In line with this, we have recently discovered that chronic microglial activation causes neurodegeneration. As highly phagocytic cells, microglia internalize nanoplastics reaching the brain. This process might in turn lead to their acute or chronic activation, thereby triggering neurological disorders. In NanoGlia, we will use rodent animal models to investigate behavioural as well as cellular and molecular changes in the brain that occur upon ingestion of nanoplastics. We will further determine nanoplastics-induced developmental reprogramming events in fetal microglia that may influence brain organogenesis and function. Understanding how nanoplastics triggers microglial activation during embryogenesis and postnatal stages and whether this immune activation leads to permanent changes in brain development and function will reveal ground-breaking mechanistic insights into the environmentally triggered pathogenesis of neurological disorders.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
53113 Bonn
Germania