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Sarcopenia, the progressive loss of muscle mass and function, universally affects older adults and is closely associated with frailty and reduced quality of life. Despite the inevitable consequences of sarcopenia and its relevance to healthspan, no pharmacological therapies are currently available. Ghrelin is a gut‐released hormone that increases appetite and body weight through acylation. Acylated ghrelin activates its receptor, growth hormone secretagogue receptor 1a (GHSR1a), in the brain by binding to it. Studies have demonstrated that acyl and unacylated ghrelin (UnAG) both have protective effects against acute pathological conditions independent of receptor activation. Here, we investigated the long‐term effects of UnAG in age‐associated muscle atrophy and contractile dysfunction in mice. Four‐month‐old and 18‐month‐old mice were subjected to either UnAG or control treatment for 10 months. UnAG did not affect food consumption or body weight. Gastrocnemius and quadriceps muscle weights were reduced by 20%–30% with age, which was partially protected against by UnAG. Specific force, force per cross‐sectional area, measured in isolated extensor digitorum longus muscle was diminished by 30% in old mice; however, UnAG prevented the loss of specific force. UnAG also protected from decreases in mitochondrial respiration and increases in hydrogen peroxide generation of skeletal muscle of old mice. Results of bulk mRNA‐seq analysis and our contractile function data show that UnAG reversed neuromuscular junction impairment that occurs with age. Collectively, our data revealed the direct role of UnAG in mitigating sarcopenia in mice, independent of food consumption or body weight, implicating UnAG treatment as a potential therapy against sarcopenia. [ABSTRACT FROM AUTHOR]

Peripheral nerve damage is a critical disorder causing disability of locomotion. The aim of the study was to clarify the effects of testosterone and tacrolimus on the gastrocnemius muscle following sciatic injury. The study was done on 20 rats (n = 5 in each group) whose left sciatic nerve was crushed for 10 s. The sham group (S) of animals received no medicine; the testosterone group (Tes) received testosterone (5 mg/kg, s.c.); the tacrolimus group (Tac): received tacrolimus (5 mg/kg, p.o.); the testosterone and tacrolimus group (Tes+Tac) received testosterone (5 mg/kg, s.c.) and tacrolimus (5 mg/kg, p.o.) daily for four weeks. The gastrocnemius was assessed by gross observation of the plantar surface of paws; the pelvic limb mass muscle and the muscle diameter ratio of the left pelvic limb to the right one by ultrasonography. The gastrocnemius muscle index (GMI) of the left and right pelvic limb, muscle colour, and pathologic changes were also studied. Pathology study of the gastrocnemius included fatty infiltration, muscle atrophy, presence of inflammatory cells and fibrosis formation. Heel redness and swelling were seen in group Tac. No significant difference was found in the GMI between the Tes and S groups (P > 0.01); its value was higher than in the Tes+Tac and Tac groups (P < 0.01). One rat in group Tes had fatty infiltration grade II. Inflammatory cells were grade I in group Tes but fibrosis formation was grade I in group Tes+Tac. Our results show that tacrolimus and testosterone administration may shorten sciatic nerve regeneration time. Testosterone may diminish gastrocnemius muscle atrophy after sciatic nerve crush. [ABSTRACT FROM AUTHOR]

Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) encompasses a group of disorders with loss of spinal motor neurons.The report describes the neuropathological findings including brain and spinal cord at autopsy in a five-and-half-month-old boy with suspected type 1 SMA. The anterior motor neurons, Clarke's column at all the levels of spinal cord showed neuronal loss and degeneration while neurons at all the deep grey nuclei were preserved apart from variable degree anoxic changes. Skeletal muscle biopsy revealed features of neurogenic atrophy consistent with SMA. A differential diagnosis like storage disorders was excluded using electron microscopy. No extra-neural manifestations were seen. Neuropathological features at autopsy have seldom been reported in the literature. [ABSTRACT FROM AUTHOR]

Introduction: Botulinum toxin A (BoNTA) is routine treatment for hypertonicity in children with cerebral palsy (CP).Methods: This single-blind, prospective, cross-sectional study of 10 participants (mean age 11 years 7 months) was done to determine the relationship between muscle histopathology and BoNTA in treated medial gastrocnemius muscle of children with CP. Open muscle biopsies were taken from medial gastrocnemius muscle and vastus lateralis (control) during orthopedic surgery.Results: Neurogenic atrophy in the medial gastrocnemius was seen in 6 participants between 4 months and 3 years post-BoNTA. Type 1 fiber loss with type 2 fiber predominance was significantly related to the number of BoNTA injections (r = 0.89, P < 0.001).Conclusions: The impact of these changes in muscle morphology on muscle function in CP is not clear. It is important to consider rotating muscle selection or injection sites within the muscle or allowing longer time between injections. [ABSTRACT FROM AUTHOR]

Spinal nerve L5/L6 ligation (SNL) in rats has become the standard for mechanistic studies of peripheral neuropathy and screening for novel analgesics. Conventional SNL in our hybrid mice resulted in a wide range of allodynia. Anatomical evaluation indicated that a variable number of lumbar vertebrae existed, resulting in L4/L5 or L5/L6 being ligated. Surprisingly, L4/L5 ligation did not result in ipsilateral hind limb paralysis and produced robust allodynia. Following a recent report that the mouse L4 neural segment is homologous with rat L5 we generated L4, L5 or both L4 and L5 (L4/L5) ligations in C57 mice after establishing a modified set of surgical landmarks. In contrast to rats, L4 ligation in these mice did not result in hind limb paralysis. Robust allodynia was observed in all three ligation groups. Nerve degeneration confirmed that L4 and L5, respectively, are primary contributors to the tibial and sural branches of the sciatic nerve in mice. A larger von Frey sensitive area reflected the wider distribution of Wallerian degeneration in the hindlimb of L4- compared to L5-ligated mice. Ligation of mouse L4 and L5 spinal nerves produces consistent, robust neuropathic pain behaviors and is suitable as a model for investigating mechanisms of neuropathic pain and for testing of novel analgesics. Gabapentin, used as a validation drug in neuropathic pain models and as a reference compound for novel analgesics, significantly reduced allodynia in the mice tested (L4/L5 ligations). Given the ease of surgery, robust allodynia, and larger von Frey sensitive area, we conclude that combined ligation of spinal nerves L4 and L5 optimizes the SNL model in mice. [ABSTRACT FROM AUTHOR]

Recurrent laryngeal neuropathy (RLN, laryngeal hemiplegia, laryngeal paralysis, 'roaring') is common in the equine industry with a prevalence ranging from 2.6-11% in light breeds (Raphel 1982; Lane 1987; Morris and Seeherman 1990) up to 38% in draught breeds (Brakenhoff et al. 2006; Perkins et al. 2009). There are a number of different surgical treatments currently available and more being developed. This article aims to discuss factors affecting choice of treatment and then provide an evidence-based approach to describe surgical approaches, success rates and morbidity. Specific details of surgical methods are not given as they are readily available in surgical textbooks (Stick 2006; McGorum et al. 2007). [ABSTRACT FROM AUTHOR]

Introduction: Brachial diplegia is a clinical term used to describe weakness restricted to the upper extremities. We report a case of brachial diplegia associated with West Nile virus infection. Methods: A 48-year-old man developed severe painless bilateral upper extremity weakness within a few weeks of a flu-like illness. Results: Clinical examination revealed marked periscapular, shoulder girdle, and humeral muscle atrophy and bilateral scapular winging, with near symmetrical bilateral hypotonic upper extremity weakness. This was associated with clinical signs of an encephalomyelopathy without cognitive or sensory deficits. Electrophysiological studies demonstrated a subacute disorder of motor neurons, their axons or both, involving the cervical and thoracic myotomes, with ongoing denervation. Serological studies confirmed recent West Nile virus (WNV) infection. Gradual improvement occurred following conservative supportive therapies. Conclusions: Progressive brachial diplegia is a rare neuromuscular presentation of WNV neuroinvasive disease. This case report adds to the clinical spectrum of WNV-induced neurologic sequelae. Muscle Nerve 45: 900-904, 2012 [ABSTRACT FROM AUTHOR]

Neurogenic atrophy refers to the loss of muscle mass and function that results directly from injury or disease of the peripheral nervous system. Individuals with neurogenic atrophy may experience reduced functional status and quality of life and, in some circumstances, reduced survival. Distinct pathological findings on muscle histology can aid in diagnosis of a neurogenic cause for muscle dysfunction, and provide indicators for the chronicity of denervation. Denervation induces pleiotypic responses in skeletal muscle, and the molecular mechanisms underlying neurogenic muscle atrophy appear to share common features with other causes of muscle atrophy, including activation of FOXO transcription factors and corresponding induction of ubiquitin-proteasomal and lysosomal degradation. In this review, we provide an overview of histologic features of neurogenic atrophy and a summary of current understanding of underlying mechanisms. [ABSTRACT FROM AUTHOR]