Effects of motor deprivation on neurogenesis and muscle-derived neurotropic factors

The positive role of exercise in individuals affected by neurologic dis- eases was recently brought to light (Okonkwo et al. 2014). On the contrary, both astronauts and patients affected by movement-limiting pathologies face impairment in muscle and brain performance. More- over, recent evidences suggest that myokines released by exercising muscles affect the expression of brain derived neurotrophic factors (Phillips et al. 2014). The purpose of this work is to study how muscular inactivity affects neurogenesis and the factors that are involved in the interaction between the muscle and the neurogenic areas. We plan to study the effect of motor deprivation using a well-established ground based model: the hindlimb unloading model (HU). Four-month-old male C57BL/6 mice were randomly selected and assigned to control (CTRL) or HU groups. The unloading lasted 14 days. At the end of the suspen- sion, gastrocnemius (GAS), soleus (SOL) muscle and brain were dissected and processed for the appropriate experimental procedure. Various neurogenic regions of the mice central nervous system (CNS) were isolated and the evaluation of the proliferative capacity of neuronal stem cells (NSCs) was performed in cultures obtained from HU and CTRL mice. Signals involved in controlling metabolism were studied in both muscles and brain. Muscle expression of fibronectin type III domain-containing protein 5 (FNDC5), which seems to play a role in regulating brain-derived neurotrophic factor (BDNF) production in CNS (Wrann et al. 2013), was also assessed. Preliminary results indicate that HU NSCs have a reduced capacity to proliferate and differentiate compared to CTRL. A reduction of PGC1alfa and FNDC5 expression in HU SOL was found. The study reveals that motor deprivation impairs neurogenesis and muscle neurotrophic factors expression.