Long-Term Evaluation of Functional Outcomes Following Rat Volumetric Muscle Loss Injury and Repair
Tissue-engineered muscle repair (TEMR) technology is used to facilitate the regeneration of muscle by providing a favorable microenvironment for regenerative growth. This is done by seeding muscle progenitor cells (MPCs) onto a porcine bladder acellular matrix (BAM), which is then implanted into the animal. Although tissue-engineered constructs are a good restorative option for volumetric muscle loss (VML) injuries, the variability between different muscles poses a challenge in creating fully compatible constructs. This study focuses on improving the matching geometry of TEMR to the TA muscle, specifically, in the rat animal model. Using Aurora’s 1305A 3-in-1 Whole Animal System, an in vivo analysis of peak isometric torque was conducted. At 6 months post VML injury, 67% of TEMR-implanted rats showed significantly greater peak isometric torque compared to other treatment groups. Moreover, 38% of TEMR responders reached approximately 90% of the maximum force production, thus demonstrating near full recovery. In addition to functional assessment, the authors conducted histological and immunofluorescence analyses. Fiber cross sectional area (FCSA) was quantified in both the experimental and control TA muscles of maximum responder rats. It was found that the median FCSA was lower in the experimental TA muscles than in the TA muscles of the control leg. Vascularization and macrophage counts were also assessed, although no significant differences were found. This study highlights the importance of adapting and improving existing tissue engineering technology to allow for optimal treatment of VML injuries in various muscles.
Olfactory and Neuromodulatory Signals Reverse Visual Object Avoidance to Approach in Drosophila
Sensory plasticity in insects is mediated by behaviour-regulating biogenic amines. Some of these regulated behaviours include olfactory learning, aggression, and feeding. In Drosophila melanogaster, octopamine influences flight patterns and the response of motion-detecting neurons. This study analyzed both odor- and optogenetic-induced flight patterns using a flight simulator and odour delivery system. In addition to this, Aurora’s 200B miniPID sensor was used to at the beginning of each experiment to confirm air/odour at the location of the fly. In odourless air, it was found that the flies steered toward a vertical bar, which may mimic a plant stalk, but avoided a small box. It is thought that the small box may appear to be threatening but could also appear to be food. As such, they tested the animals’ response to each object in the presence of odours considered attractive to D. melanogaster. When Apple Cider Vinegar or ethanol odourant was added to the air, flies approached the small box that was previously avoided, and more strongly approached the vertical bar. However, in the presence of the odourant benzaldehyde, an odour that flies avoid, the flies displayed avoidance of the small object but continued to approach the vertical bar. These results suggest that visual valence reversal is produced by attractive odourants, but not aversive odourants. To elucidate how olfactory signals are coupled with behaviours, the authors tested whether aminergic neuromodulation was involved in odour-induced visual valence reversal. Transgenic flies expressing Chrimson, a red shifted excitatory channelrhodopsin, in aminergic neurons were subjected to stimulation by Chrimson-exciting illumination. Optogenetic depolarization of octopaminergic (OA) or tyraminergic (TA) neurons by the Tdc2-Gal4 driver changed the flight response to the small box from aversion to approach. Similar avoidance reversal was seen in 15/16 flies upon Tdc2 > Chrimson activation and in flies expressing Chrimson in T4 and T5 neurons. Taken together, this study provides insight into a model for multisensory processing in which attractive odors stimulate Tdc2 release, thus increasing response gain of the motion vision pathway.
Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis
Gut microbiota influence the development of several chronic diseases including obesity, diabetes, and allergies. Recent studies suggest that an imbalance of gut microbiota may also influence muscle metabolism and contribute to muscle atrophy. This study focused on characterizing the impact of gut microbiota depletion on skeletal muscle by analyzing mice treated with gut-microbiota depleting antibiotics (ABT), mice treated with antibiotics followed by natural reseeding of microbiota (NAT), and control mice (CTL). Each group underwent running tests, where no differences were found in maximal aerobic velocity between each group. For the “Limit time to exhaustion during submaximal running test”, Tlim was significantly lower at day 9 than day 0 in both ATB and NAT mice. However, Tlim at day 19 was lower than day 0 in only the ATB group. Ex vivo contractile tests were then conducted using Aurora’s 305C Dual-Mode Muscle Lever and 701C High-Power Stimulator. EDL maximal strength was unaffected by the running tests; however, EDL muscle fatigue index was significantly reduced in ATB mice when compared with CTL and NAT mice. To investigate the role of gut microbiota on muscular glucose homeostasis, the authors analyzed markers linked to glucose metabolism in the gut-skeletal muscle. Levels of fasting-induced adipocyte factor (Fiaf) were significantly higher in the ATB group. In addition to this, free fatty acid receptor 3 (Gpr41) expression decreased. Following natural reseeding of the NAT group, increased levels of Gpr41 mRNA were observed when compared with the ABT group. Ileum muscle glycogen was also found to be significantly lower in ATB mice. These results highlight the interplay between gut microbiota and skeletal muscle. This study also provides insight into microbiome-based strategies for muscle therapy.