Key pointsr Muscle fibre cross sectional area is enhanced with massage in the form of cyclic compressive loading during regrowth after atrophy.r Massage enhances protein synthesis of the myofibrillar and cytosolic, but not the mitochondrial fraction, in muscle during regrowth. r Massage in the form of cyclic compressive loading is a potential anabolic intervention during muscle regrowth after atrophy.Abstract Massage, in the form of cyclic compressive loading (CCL), is associated with multiple health benefits, but its potential anabolic effect on atrophied muscle has not been investigated. We hypothesized that the mechanical activity associated with CCL induces an anabolic effect in skeletal muscle undergoing regrowth after a period of atrophy. Fischer-Brown Norway rats at 10 months of age were hindlimb unloaded for a period of 2 weeks. The rats were then allowed reambulation with CCL applied at a 4.5 N load at 0.5 Hz frequency for 30 min every other day for four bouts during a regrowth period of 8 days. Muscle fibre cross sectional area was enhanced by 18% with massage during regrowth compared to reloading alone, and this was accompanied by elevated myofibrillar and cytosolic protein as well as DNA synthesis. Focal adhesion kinase phosphorylation indicated that CCL increased mechanical stimulation, while a higher number of Pax7 + cells likely explains the elevated DNA synthesis. Surprisingly, the contralateral non-massaged limb exhibited a comparable 17% higher muscle fibre size compared to reloading alone, and myofibrillar protein synthesis, but not DNA synthesis, was also elevated. We conclude that massage in the form of CCL induces an anabolic response in muscles regrowing after an atrophy-inducing event. We suggest that massage can be used as an intervention to aid in the regrowth of muscle lost during immobilization.

Serotonin modulates various physiological processes and behaviors. This study investigates the role of 5-HT in locomotion and feeding behaviors as well as in modulation of sensory-motor circuits. The 5-HT biosynthesis was dysregulated by feeding Drosophila larvae 5-HT, a 5-HT precursor, or an inhibitor of tryptophan hydroxylase during early stages of development. The effects of feeding fluoxetine, a selective serotonin reuptake inhibitor, during early second instars were also examined. 5-HT receptor subtypes were manipulated using RNA interference mediated knockdown and 5-HT receptor insertional mutations. Moreover, synaptic transmission at 5-HT neurons was blocked or enhanced in both larvae and adult flies. The results demonstrate that disruption of components within the 5-HT system significantly impairs locomotion and feeding behaviors in larvae. Acute activation of 5-HT neurons disrupts normal locomotion activity in adult flies. To determine which 5-HT receptor subtype modulates the evoked sensory-motor activity, pharmacological agents were used. In addition, the activity of 5-HT neurons was enhanced by expressing and activating TrpA1 channels or channelrhodopsin-2 while recording the evoked excitatory postsynaptic potentials (EPSPs) in muscle fibers. 5-HT2 receptor activation mediates a modulatory role in a sensory-motor circuit, and the activation of 5-HT neurons can suppress the neural circuit activity, while fluoxetine can significantly decrease the sensory-motor activity.

Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically.

Serotonin, 5-hydroxytryptamine (5-HT), plays various roles in the fruit fly, Drosophila melanogaster. Previous studies have shown that 5-HT modulates the heart rate in third instar larvae. However, the receptor subtypes that mediate 5-HT action in larval cardiac tissue had yet to be determined. In this study, various 5-HT agonists and antagonists were employed to determine which 5-HT receptor subtypes are responsible for the positive chronotropic effect by 5-HT. The pharmacological results demonstrate that a 5-HT2B agonist significantly increases the heart rate; however, 5-HT1A, 5-HT1B, and 5-HT7 agonists do not have a significant effect on the heart rate. Furthermore, 5-HT2 antagonist, ketanserin, markedly reduces the positive chronotropic effect of 5-HT in a dose-response manner. Furthermore, we employed genetic approaches to confirm the pharmacological results. For this purpose, we used RNA interference line to knock down 5-HT2ADro and also used 5-HT2ADro and 5-HT2BDro insertional mutation lines. The results show that 5-HT2ADro or 5-HT2BDro receptor mutations reduce the response of the heart to 5-HT. Given these results, we conclude that these 5-HT2 receptor subtypes are involved in the action of 5-HT on the heart rate in the larval stage.