FLAVIA FORCONI

Dottoressa di ricerca

ciclo: XXXV


supervisore: Emanuele Rizzuto/ Antonio Musarò

Titolo della tesi: Development of innovative techniques, experimental devices and testing protocols for the measurement of muscle and neuromuscular junction functionality in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) remains an invariably fatal disease, in which neuromuscular junction (NMJ) functionality is strongly impaired. To this, the aim of this research project was to develop a series of novel testing tools for a precise assessment of the altered communication between muscle and nerve in ALS progression. A novel technique for the in-situ measurement of murine Tibialis Anterior (TA) NMJ functionality in isotonic conditions was developed and validated. A novel parameter, named Isotonic Neurotransmission Failure (INF), was proposed. Results showed an increase in INF of SOD1G93A mouse TA muscles at the end-stage of the disease, highlighting, for the first time, an increased impairment of NMJ functionality in isotonic conditions. An embedded system for the measurement of 3D engineered skeletal muscle tissues’ contractility with a non-invasive technique was proposed. Results showed the capability of the system to not impair tissue's contractility during the entire growth, and to discriminate healthy and pathological conditions. Finally, a 3D microfluidic device was designed and realized to promote the formation of NMJ between spinal cord-derived neuronal cells and 3D engineered skeletal muscle. Results showed a good attraction between these two cells populations, paving the basis for the development of a more comprehensive 3D NMJ in-vitro model. On the other hand, since extracellular vesicles (EVs) are involved in ALS pathological proteins transportation, a series of preliminary experiments with muscle cells’ populations was carried out, with the final aim of evaluating the role of SOD1G93A mice-derived EVs on the novel experimental models here proposed. Results showed that SOD1G93A mice-derived EVs increased in number during the ALS progression, and impaired C2C12 cells’ differentiation. In conclusion, a series of novel testing tools have been developed for a precise assessment of the NMJ functionality in different models which, of note, can be also employed to unravel the mechanism behind muscle-nerve impairments in other neurodegenerative pathologies.

Produzione scientifica

11573/1656751 - 2022 - The development of an innovative embedded sensor for the optical measurement of ex-vivo engineered muscle tissue contractility
Apa, Ludovica; Cosentino, Marianna; Forconi, Flavia; Musarò, Antonio; Rizzuto, Emanuele; Del Prete, Zaccaria - 01a Articolo in rivista
rivista: SENSORS (Basel : Molecular Diversity Preservation International (MDPI), 2001-) pp. 1-15 - issn: 1424-8220 - wos: WOS:000856744500001 (2) - scopus: 2-s2.0-85138778040 (3)

11573/1656757 - 2022 - Effects of ROI positioning on the measurement of engineered muscle tissue contractility with an optical tracking method
Forconi, F.; Apa, L.; Cosentino, M.; Musaro', Antonio; Rizzuto, E.; Del Prete, Z. - 04b Atto di convegno in volume
congresso: 17th IEEE International Symposium on Medical Measurements and Applications, MeMeA 2022 (Messina)
libro: 2022 IEEE International Symposium on Medical Measurements and Applications, MeMeA 2022 - Conference Proceedings - (978-1-6654-8299-8)

11573/1632977 - 2022 - Development of a novel technique for the measurement of neuromuscular junction functionality in isotonic conditions
Forconi, F.; Apa, L.; Pisu, S.; Casola, I.; Musarò, Antonio.; Rizzuto, E.; Del Prete, Z. - 01a Articolo in rivista
rivista: CELLULAR AND MOLECULAR BIOENGINEERING (New York : Springer) pp. 255-265 - issn: 1865-5025 - wos: WOS:000779223600001 (2) - scopus: 2-s2.0-85127711682 (3)

11573/1556137 - 2021 - Electric field distribution analysis for the design of an electrode system in a 3D neuromuscular junction microfluidic device
Forconi, Flavia; Apa, Ludovica; D'alvia, Livio; Cosentino, Marianna; Rizzuto, Emanuele; Del Prete, Zaccaria - 04b Atto di convegno in volume
congresso: MeMeA 2021 - 2021 IEEE International Symposium on Medical Measurements and Application (Viertual)
libro: MeMeA 2021 - 2021 IEEE International Symposium on Medical Measurements and Applications Proceedings - (978-1-6654-1914-7)

11573/1443414 - 2020 - Optimal force evaluation for isotonic fatigue characterization in mouse Tibialis Anterior muscle
Forconi, F.; Martelli, F.; Pisu, S.; Musaro, A.; Rizzuto, E.; Del Prete, Z. - 04b Atto di convegno in volume
congresso: 15th IEEE International Symposium on Medical Measurements and Applications, MeMeA 2020 (Bari, Italy)
libro: IEEE Medical Measurements and Applications, MeMeA 2020 - Conference Proceedings - (978-1-7281-5386-5)

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