Attività del Calcio In Vivo dei Graft Striatali in un Modello di Ratto della Malattia di Huntington

Huntington's disease (HD) is a neurodegenerative disorder primarily affecting striatal function due to mutations in the Huntingtin gene. It is characterized by motor, cognitive, and psychiatric symptoms, along with cortico-striatal circuit abnormalities. Currently, there is no cure, and one proposed therapeutic approach involves replacing the vulnerable GABAergic medium spiny neurons (MSNs) in the striatum, predominantly targeted in the early stages of the disease. This project explores cell replacement strategy using rat-embryonic precursors grafts from the whole ganglionic eminence (WGE) to replace the lost MSNs population and reconstitute damaged striatal networks in a chemical rat model of HD. Specifically, it focuses on assessing graft spontaneous activity and functional integration at different time windows, through the detection of calcium signals. Results indicate that a significant portion of the engrafted cells differentiate into MSNs and interneurons. Calcium signal analysis reveals a decline in spontaneous activity over time, yet the majority of implanted cells exhibit a strong response to foot shock stimulation, suggesting functional integration. Additionally, sensory-motor function improves progressively across different post-transplantation time points in grafted rats, further supporting the idea of successful integration and functional recovery.