Cellular function of satellite cells does not play a role in muscle weakness of adult Ts1Cje mice

Abstract

Down syndrome (DS) is a genetic condition resulting from triplication of human chromosome (HSA)21. Besides intellectual disability, DS is frequently associated with hypotonia. Satellite cells are the resident cells that provides robust and remarkable regenerative capacity to the skeletal muscles, and its population size has been reported to be disease-associated. However, little is known about the population size of satellite cells in DS and the association of its intrinsic cellular functionality and hypotonia seen in DS. Here, we studied the Ts1Cje mouse, a DS murine model displays the muscle weakness characteristic. Satellite cell populations were immunostained with Pax7 and myonuclei numbers in the Ts1Cje extensor digitorum longus muscle were assessed. Their cellular function was further determined via in vitro assay in high-serum conditioned medium. Subsequently, the in vitro self-renewal, proliferative, and differentiation activities of these myogenic precursor cells were assessed after 24, 48, and 72h using Pax7, MyoD, and Ki67 immunomarkers. Our results showed that the population and functionality of Ts1Cje satellite cell did not differ significantly when compared to the wildtype cells isolated from disomic littermates. In conclusion, our findings indicated that intrinsic cellular functionality of the satellite cells, do not contribute to muscle weakness in Ts1Cje mouse.

Transcriptomic profiling of skeletal muscle from the Ts1Cje mouse model of Down syndrome suggests dysregulation of trisomic genes associated with neuromuscular junction signaling, oxidative stress and chronic inflammation

“…Downregulation of Ifnar1 and Ifnar2 are expected to reduce JAK-STAT signalling pathway which in turn would promote myoblast renewal and regeneration processes [85]. However, a previous study of skeletal muscle stem cells (SMSCs) derived from Ts1Cje and control mice of the same age did not show any differences in the number SMSC as well as their differentiation capability in vitro [86]. Although the finding suggests no apparent differences in myogenesis during normal physiological state of Ts1CJe muscles, it does not preclude the potential involvement of Ifnar1 and Ifnar2 via JAK-STAT signalling pathway during early skeletal muscle development or regeneration state which will become obvious in aging subjects or during muscle injuries.…”

Research beyond biomedical confines: towards better mental health and well-being for all

“…The presence of physical disabilities, for example, can lead to poor mental health as a result of social factors such as disability-related discrimination and heighten risk for the development of mental disorders such as depression, anxiety and post-traumatic stress disorder [14]. Our review of past articles indicated that contributors to NeurosciRN are keen to understand and develop interventions for a wide variety of health conditions closely associated with functional disability ranging from stroke [15,16], to epilepsy [17][18][19][20][21], to neurodegenerative diseases [22] as well as Down's syndrome [23][24][25]. 'Functional disability' refers to how people with health conditions are prevented from engaging and participating in activities, roles and other aspects of their lives, which are of value to them.…”