Descrizione del progetto
Innervazione della fascia e controllo del danno d’organo
La fascia connettivale è il tessuto più esteso del corpo e delimita la pelle e tutti gli organi. Le ragioni per cui questa barriera meccanica è popolata da cellule immunitarie e innervata da neuroni sensoriali e simpatici non sono chiare. Il progetto NEUROFASCIA, finanziato dal CER, propone che la fascia costituisca una piattaforma sensoriale per rilevare i danni ai tessuti e comunichi informazioni al cervello per avviare meccanismi correttivi e attività immunitarie. I risultati preliminari indicano che la depressione cronica nei topi o l’attivazione optogenetica delle innervazioni simpatiche della fascia inducono cambiamenti immunitari nella fascia. Gli obiettivi del progetto comprendono la caratterizzazione dell’innervazione della fascia e delle cellule immunitarie residenti, lo studio della manifestazione dell’infiammazione della fascia nel cervello e la comprensione del controllo neurale della fascia e del suo stato immunitario.
Obiettivo
The fascia is the largest tissue in the body, yet most of us never heard of it. This connective tissue delineates the skin, surrounds muscles, and closely envelops all organs. Clinically, it is mainly considered a mechanical barrier separating organs and muscles. But why should a simple barrier be populated with immune cells and receive extensive innervation by sensory and sympathetic neurons?
Here we propose that the fascia generates a sensory platform that detects damage to the tissues it envelops and communicates this information to the brain which in turn, initiates corrective programs and modulates immune activity. Our preliminary results support this hypothesis indicating that chronic depression in mice and direct optogenetic activation of sympathetic fascia innervations induce immune changes in the fascia.
We propose three major aims:
A) Characterization: Identify the anatomical and genetic characteristics of fascia innervation and fascia resident immune cells
B) Function: Determine how fascia inflammation is represented in the brain and how it affects pain responses
C) Modulation: Demonstrate how neural control of the fascia affects this tissue and its immune state
My multidisciplinary background uniquely positions me to study this novel aspect of brain-body communication. We will use viral tracing and spatial transcriptomics to characterize the fascia’s innervation; optogenetics to locally control neurons in the fascia; chemogenetics to manipulate brain activity; and high-dimensional immune characterization to establish the immunological outcomes in the fascia.
NEUROFASCIA has the potential to transform our understanding of brain-immune communication and open new therapeutic avenues for disease such as myofascial pain syndrome, endometriosis, and fibromyalgia, which are accompanied by low-grade inflammation and altered fascia innervation.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
32000 Haifa
Israele