Effects of prolonged vibration to the flexor carpi radialis muscle on intracortical excitability.

Prolonged local vibration (LV) can induce neurophysiological adaptations thought to be related to long-term potentiation or depression. Yet, how changes in intracortical excitability may be involved remains to be further investigated as previous studies reported equivocal results. We therefore investigated the effects of 30 min of LV applied to the right flexor carpi radialis muscle (FCR) on both short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). SICI and ICF were measured through transcranial magnetic stimulation before and immediately after 30 min of FCR LV (vibration condition) or 30 min of rest (control condition). Measurements were performed during a low-intensity contraction (n = 17) or at rest (n = 7). No significant SICI nor ICF modulations were observed, whether measured during isometric contractions or at rest (p = 0.2). Yet, we observed an increase in inter-individual variability for post measurements after LV. In conclusion, while intracortical excitability was not significantly modulated after LV, increased inter-variability observed after LV may suggest the possibility of divergent responses to prolonged LV exposure.

Design and Evaluation of Autophagy-Inducing Particles for the Treatment of Abnormal Lipid Accumulation.

Autophagy is a fundamental housekeeping process by which cells degrade their components to maintain homeostasis. Defects in autophagy have been associated with aging, neurodegeneration and metabolic diseases. Non-alcoholic fatty liver diseases (NAFLDs) are characterized by hepatic fat accumulation with or without inflammation. No treatment for NAFLDs is currently available, but autophagy induction has been proposed as a promising therapeutic strategy. Here, we aimed to design autophagy-inducing particles, using the autophagy-inducing peptide (Tat-Beclin), and achieve liver targeting in vivo, taking NAFLD as a model disease. Polylactic acid (PLA) particles were prepared by nanoprecipitation without any surfactant, followed by surface peptide adsorption. The ability of Tat-Beclin nanoparticles (NP T-B) to modulate autophagy and to decrease intracellular lipid was evaluated in vitro by LC3 immunoblot and using a cellular model of steatosis, respectively. The intracellular localization of particles was evaluated by transmission electron microscopy (TEM). Finally, biodistribution of fluorescent NP T-B was evaluated in vivo using tomography in normal and obese mice. The results showed that NP T-B induce autophagy with a long-lasting and enhanced effect compared to the soluble peptide, and at a ten times lower dose. Intracellular lipid also decreased in a cellular model of NAFLD after treatment with T-B and NP T-B under the same dose conditions. Ultrastructural studies revealed that NP T-B are internalized and located in endosomal, endolysosomal and autolysosomal compartments, while in healthy and obese mice, NP T-B could accumulate for several days in the liver. Given the beneficial effects of autophagy-inducing particles in vitro, and their capacity to target the liver of normal and obese mice, NP T-B could be a promising therapeutic tool for NAFLDs, warranting further in vivo investigation.