Motor Unit Fatigability following Chronic Carnosine Supplementation in Aged Rats.

Studies suggest that carnosine (beta-alanyl-L-histidine) is effective in treating neuromuscular diseases associated with aging, but there is still a need to clarify its role in motor units (MUs) function during aging. In this study, 40 male Wistar rats aged 15 months were randomly assigned to a control or to two experimental groups in which 0.1% carnosine supplementation was performed for 10 or 34 weeks. After 34 weeks, we examined fast fatigable (FF), fast fatigue-resistant (FR) and slow (S) MUs' force properties and fatigability, as well as antioxidant potential, advanced glycation end products, activity of enzymes, and histidyl dipeptides content in the medial gastrocnemius muscle. Short- and long-term carnosine supplementation maintained the force of FF MUs at a higher level during its rapid decline seen from the initial 10 to 70 s of the fatigue test. In FF, especially long-term, and in FR MUs, especially short-term, carnosine supplementation resulted in less rapid force decline during the initial 70 s of the second fatigue protocol. Carnosine supplementation did not change muscle antioxidant potential and mortality rate (~35% in all groups), nor muscle mass with aging. Moreover, instead of the expected increase, a decrease in histidyl dipeptides by ~30% in the red portion of medial gastrocnemius muscle after long-term supplementation was found. After chronic carnosine supplementation, the specific changes in fatigue resistance were observed in FF and FR units, but not in S MU types that were not accompanied by an improvement of antioxidant potential and activity of glycolytic or oxidative enzymes in aged rats. These observations indicate that carnosine supplementation during aging may generate different physiological adaptations which should be considered as an important factor when planning treatment strategies.

Long-lasting increase in axonal excitability after epidurally applied DC.

Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2) the increase in the excitability appears within seconds, 3) lasts for >1 h, and 4) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect.NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result in more effective pain control and the return of impaired motor functions.

Role of histidyl dipeptides in contractile function of fast and slow motor units in rat skeletal muscle.

The physiological role of the muscle histidyl dipeptides carnosine and anserine in contractile function of various types of muscle fibers in vivo is poorly understood. Ten adult male Wistar rats were randomly assigned to two groups: control and supplemented for 10 wk with beta-alanine, the precursor of carnosine (∼640 mg·kg body wt(-1)·day(-1)). Thereafter, contractile properties and fatigability of isolated fast fatigable (FF), fast resistant to fatigue (FR), and slow motor units (MUs) from the medial gastrocnemius were determined in deeply anaesthetized animals. The fatigue resistance was tested with a 40-Hz fatigue protocol followed by a second protocol at 40 Hz in fast and 20 Hz in slow units. In the supplemented rats, histidyl dipeptide concentrations significantly increased (P < 0.05) by 25% in the red portion of the gastrocnemius, and carnosine increased by 94% in the white portion. The twitch force of FF units and maximum tetanic force of FR units were significantly increased (P < 0.05), and the half-relaxation time was prolonged in slow units (P < 0.05). FF units showed less fatigue during the first 10 s, and FR units showed higher forces between 10 and 60 s during the 40-Hz fatigue test. In slow units, forces declined less during the first 60 s of the 20-Hz test. In conclusion, this in vivo experiment demonstrates that an elevation in muscle histidyl dipeptide content elicits beneficial changes in MU contractile characteristics and fatigue resistance. Carnosine and anserine seem to play an important yet divergent role in various MUs.