Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS.

Amyotrophic Lateral Sclerosis (ALS) is a neural disorder gradually leading to paralysis of the whole body. Alterations in superoxide dismutase SOD1 gene have been linked with several variants of familial ALS. Here, we investigated a transgenic (Tg) cloned swine model expressing the human pathological hSOD1G93A allele. As in patients, these Tg pigs transmitted the disease to the progeny with an autosomal dominant trait and showed ALS onset from about 27 months of age. Post mortem analysis revealed motor neuron (MN) degeneration, gliosis and hSOD1 protein aggregates in brainstem and spinal cord. Severe skeletal muscle pathology including necrosis and inflammation was observed at the end stage, as well. Remarkably, as in human patients, these Tg pigs showed a quite long presymptomatic phase in which gradually increasing amounts of TDP-43 were detected in peripheral blood mononuclear cells. Thus, this transgenic swine model opens the unique opportunity to investigate ALS biomarkers even before disease onset other than testing novel drugs and possible medical devices.

Acute and cumulative effects of rTMS on behavioural and EMG parameters in Focal Hand Dystonia.

Previous studies suggest that low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) over contralateral premotor cortex (PMC) might ameliorate Focal Hand Dystonia (FHD) symptoms. In the present study behavioral and muscle activity outcomes were explored in a patient with FHD following a single and multiple sessions of rTMS. The patient's behavior was assessed on handwriting tasks, while surface EMG signals were recorded. In Experiment 1 evaluations were performed before and after one session of active and sham 1Hz rTMS over contralateral PMC. In Experiment 2, evaluations were performed before and after six sessions of the same treatment. In Experiment 1 active rTMS improved the patient's performance, although the EMG amplitude did not change. In Experiment 2, the patient showed an improvement of performance along with a decrease of 20% in the EMG amplitude. These results demonstrated that a single session of rTMS ameliorated the patient's performance, while multiple sessions were necessary to reduce muscles activity.

Higher Neuromuscular Manifestations of Fatigue in Dynamic than Isometric Pull-Up Tasks in Rock Climbers.

Neuromuscular assessment of rock climbers has been mainly focused on forearm muscles in the literature. We aimed to extend the body of knowledge investigating on two other upper limb muscles during sport-specific activities in nine male rock climbers. We assessed neuromuscular manifestations of fatigue recording surface electromyographic signals from brachioradialis and teres major muscles, using multi-channel electrode arrays. Participants performed two tasks until volitional exhaustion: a sequence of dynamic pull-ups and an isometric contraction sustaining the body at half-way of a pull-up (with the elbows flexed at 90°). The tasks were performed in randomized order with 10 minutes of rest in between. The normalized rate of change of muscle fiber conduction velocity was calculated as the index of fatigue. The time-to-task failure was significantly shorter in the dynamic (31 ±10 s) than isometric contraction (59 ±19 s). The rate of decrease of muscle fiber conduction velocity was found steeper in the dynamic than isometric task both in brachioradialis (isometric: -0.2 ±0.1%/s; dynamic: -1.2 ±0.6%/s) and teres major muscles (isometric: -0.4±0.3%/s; dynamic: -1.8±0.7%/s). The main finding was that a sequence of dynamic pull-ups lead to higher fatigue than sustaining the body weight in an isometric condition at half-way of a pull-up. Furthermore, we confirmed the possibility to properly record physiological CV estimates from two muscles, which had never been studied before in rock climbing, in highly dynamic contractions.