Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD), the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3β (GSK-3β) is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3β, an inactive form of GSK-3β, suggesting that glucocorticoids affect GSK-3β activity. We then investigated whether GSK-3β inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3β: pharmacological inhibition with LiCl and GSK-3β gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3β inhibition attenuated glucocorticoid-induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3β in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3β may be a strategy for preventing glucocorticoid-induced muscle degeneration.

The aberrant deposition of β-amyloid (Aβ) is closely linked to the pathogenesis and development of Alzheimer's disease (AD). MiR-16 was abnormally downregulated and may be related to the development of AD. However, the functional role and molecular mechanism of miR-16 in AD pathogenesis are still not well elucidated. The expressions of miR-16 and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA and protein levels in AD brain tissues and Aβ-treated PC12 cellular AD model were examined by qRT-PCR and western blot analyses. Luciferase reporter assay was used to verify the potential target of miR-16. The cell viability, apoptosis, and caspase-3 activity in PC12 cells were determined by the MTT assay, flow cytometry analysis, and caspase-3 activity assay, respectively. Downregulation of miR-16 and upregulation of BACE1 existed in AD tissues and the cellular AD model of PC12. In addition, miR-16 directly suppressed BACE1 expression. Moreover, miR-16 overexpression and BACE1 knockdown facilitated Aβ-induced cell toxicity, apoptosis, and caspase-3 activity in N2a cells, which was partially eliminated by overexpression of BACE1. In contrast, BACE1 knockdown reversed the miR-16 inhibition-mediated inhibitory effect on Aβ-induced cell toxicity, apoptosis, and caspase-3 activity in PC12 cells. Collectively, miR-16 attenuated Aβ-induced neurotoxicity through targeting BACE1 in an Aβ insult cellular AD model, providing a potential therapeutic target for AD treatment.

Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness (DOC). However, these treatments require invasive procedures. This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice. Through the delivery of ultrasound energy to the ventral tegmental area, mice were aroused from an unconscious, anaesthetized state in this study, and this process was controlled by adjusting the ultrasound parameters. The mice in the sham group under isoflurane-induced, continuous, steady-state general anaesthesia did not regain their righting reflex. On insonation, the emergence time from inhaled isoflurane anaesthesia decreased (sham: 13.63±0.53 min, ultrasound: 1.5±0.19 min, p<0.001). Further, the induction time (sham: 12.0±0.6 min, ultrasound: 17.88±0.64 min, p<0.001) and the concentration for 50% of the maximal effect (EC50) of isoflurane (sham: 0.6%, ultrasound: 0.7%) increased. In addition, ultrasound stimulation reduced the recovery time in mice with traumatic brain injury (sham: 30.38±1.9 min, ultrasound: 7.38±1.02 min, p<0.01). This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.

No abstract