Neuromuscular Research Articles

EVs move messes, not messages, at the synapse.

Extracellular vesicles are known for intercellular signaling roles but can also serve to simply dispose of unwanted cargoes. In this issue, Bostelman and Broihier discuss new work from Rodal and colleagues (https://doi.org/10.1083/jcb.202405025) that refutes prior work by showing that extracellular vesicles at Drosophila neuromuscular junctions are not required for signaling and instead likely serve a proteostasis role.

Experimental investigation for the influence mechanism of air intake method and humidity level on performance of proton exchange membrane fuel cells

As pivotal component of hydrogen fuel cell vehicles (HFCVs), proton exchange membrane fuel cells (PEMFCs) play a crucial role in determining performance and energy efficiency of HFCVs. In this study, comprehensive bench tests of fuel cell stack and electrochemical impedance spectroscopy (EIS) tests of single cells were conducted, and influence mechanisms of air intake methods and humidity levels on performance of stack and single cells at different locations were analyzed in depth. The results indicate that counter-flow inlet method exhibits superior voltage output performance and stability across various relative humidity (RH) and current densities (CDs). A moderate increase in RH can mitigate performance degradation, but excessive humidity can lead to flooding. When RH is increased to 60%, the voltage difference between co-flow and counter-flow of fuel cell stack does not exceed 0.05 V at 1.6 A/cm2. Meanwhile, the performance of cells near inlet end plate is consistently worse than those farther away under different inlet conditions. In addition, the performance trend of single cells in serpentine channels aligns with that of fuel cell stack, underscoring strong adaptability of mechanisms influencing performance under different conditions. These findings provide theoretical guidance and data support for optimizing performance and preventing failures in PEMFCs.

Spinal magnetic resonance imaging in cats: differences in clinical significance of intervertebral disk extrusion, intervertebral disk protrusion, and degenerative lumbosacral stenosis.

To determine the occurrence of degenerative changes affecting the vertebral column in cats, assess their clinical significance, and determine the occurrence in cats with intervertebral disk herniation compared to other spinal diseases. 114 client-owned cats. Hospital records were retrospectively reviewed for cats with suspected myelopathy that had undergone spinal MRI. Signalment; history; neurological examination; neurolocalization; primary diagnosis; presence, type, and location of intervertebral disk herniation; and presence and location of other degenerative spinal changes (intervertebral disk degeneration [IVDD], spondylosis deformans [SD], end plate changes, dorsal compressions [DC], and foraminal stenosis [FS]) were recorded. 70% of cats showed at least 1 spinal degenerative change. The most common change was IVDD, followed by SD and intervertebral disk protrusion (IVDP), while intervertebral disk extrusion (IVDE), end plate changes, DC, and FS were uncommon to rare. Primary complaint was attributed to a degenerative condition in 22% of cats, including 100% with IVDE, 9% with IVDP, and 43% with degenerative lumbosacral stenosis (DLSS). The occurrence of degenerative spinal changes and number of intervertebral disks affected by IVDD significantly increased with age and body weight. Age was positively correlated with the occurrence of SD and DLSS. Intervertebral disk degeneration, IVDP, SD, DC, and FS were more prevalent in the lumbosacral junction. Cats with IVDD were significantly more likely to show IVDE and IVDP. This study revealed that in a population of cats presenting for signs of myelopathy, IVDE was always responsible for the clinical presentation, DLSS was commonly considered incidental, and IVDP was infrequently related to neurological signs.

Effects of Cannabis sativa on the Neuromuscular System and Cognitive Behavior of Male Wistar Rats

This research investigates the influence of Cannabis sativa on the neuromuscular system and cognitive behavior of male Wistar rats. Twenty rats were randomly allocated into five groups, with Group 5 serving as the control and Groups 1 to 4 receiving oral doses of Cannabis sativa at concentrations of 100 mg/kg, 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The study employs various behavioral tests, including the Beam Walking Test, Morris Water Maze, Tail Suspension Test, Open-Field Test, and Hand Grip Test, to assess the effects of Cannabis on Wistar rats. Results from the Beam walking Test suggest that the control group (Group 5) demonstrated the best neuromuscular performance, with Group 3, (receiving 400 mg/kg), following closely. In the Morris Water Maze, Groups 1 and 5 exhibited superior results, while higher doses had a negative impact. Tail Suspension Test outcomes revealed that Group 5 displayed non-depressive behavior, while Group 4 exhibited signs of depression. The Hand Grip Test demonstrated longer duration for Groups 2 and 4, suggesting a positive impact on muscle strength compared to the control, on Open Field Test, Group 1 spent the most of the time at the center, indicating lower anxiety, whereas other groups displayed increased anxiety with higher Cannabis doses. The study highlights complex and dose-dependent effects of Cannabis on neuromuscular and cognitive parameters. Caution is advised in interpreting these findings, and further research is recommended to elucidate underlying mechanisms and explore a broader range of doses. Keywords: Cannabis sativa, cognitive function neuromuscular function

Changes in brain functional connectivity and muscle strength independent of elbow flexor atrophy following upper limb immobilization in young females.

Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to strength loss. The purpose of this study was to characterize changes in the brain and neuromuscular system in addition to muscle size following upper limb immobilization in young females. Using a within-participant, unilateral design, 12 females (age: 20.6±2.1years) underwent 14days of upper arm immobilization using an elbow brace and sling. Bilateral measures of muscle strength (isometric and isokinetic dynamometry), muscle size (magnetic resonance imaging), voluntary muscle activation capacity, corticospinal excitability, cortical thickness and resting-state functional connectivity were collected before and after immobilization. Immobilization induced a significant decline in isometric elbow flexion (-21.3±19.2%, interaction: P=0.0440) and extension (-19.9±15.7%, interaction: P=0.0317) strength in the immobilized arm only. There was no significant effect of immobilization on elbow flexor cross-sectional area (CSA) (-1.2±2.4%, interaction: P=0.466), whereas elbow extensor CSA decreased (-2.9±2.9%, interaction: P=0.0177) in the immobilized arm. Immobilization did not differentially alter voluntary activation capacity, corticospinal excitability, or cortical thickness (P>0.05); however, there were significant changes in the functional connectivity of brain regions related to movement planning and error detection (P<0.05). This study reveals that elbow flexor strength loss can occur in the absence of significant elbow flexor muscle atrophy, and that the brain represents a site of functional adaptation in response to upper limb immobilization in young females.

MuSK Antibody Positive Myasthenia Gravis Mimicking as Myositis

ABSTRACT Most common neuromuscular junction disorder is Myasthenia gravis (MG) which has variable clinical presentations. Diplopia and drooping of eyelids are the peculiarity of myasthenia gravis. Commonly disease manifests as a fluctuating weakness of skeletal muscles. Although respiratory symptoms may be the initial presenting complaint in a few patients, usually it develops during the later part of the disease course. The initial presentation of isolated prominent respiratory distress is a relatively rare presentation of myasthenia gravis unless accompanied by other clinical features. We report a 40-year-old female patient, who visited our hospital with presenting complaints of breathlessness and generalized myalgia and subsequently developed fatigable weakness during hospitalization.

Invertebrate and dinoflagellate marine toxins targeting signaling and key components of the skeletal neuromuscular system of vertebrates

Invertebrate and dinoflagellate marine toxins targeting signaling and key components of the skeletal neuromuscular system of vertebrates

Role of minimal F-wave latency in the electrodiagnosis of polyneuropathy

Background and objective: Polyneuropathy is a debilitating condition that causes damage to more than two peripheral nerves in the body. The objective of this research was to detect the role of minimal F-wave latency as compared with other nerve conduction parameters for the electro-diagnosis of polyneuropathies. Methods: In this descriptive, prospective cross-sectional study, 80 consecutive patients with clinical diagnosis of polyneuropathy (both acute and chronic) between July and December 2023, presenting to the Neurology Department at King Edward Medical University were enrolled. Patients with clinical diagnosis of cervical/lumbar radiculopathies, plexopathies, compressive myelopathy , neuromuscular junction diseases, motor neuron disorders, or localized neuropathies were excluded from this research. NCS and EMG were carried out using conventional procedure. The results were recorded in the predesigned pro forma along with the history and demographic information. Statistical software SPSS 25.0 was used for the analysis of the recorded data. Results: F-wave abnormality was detected in 57 (71.3%) for median nerve, 57 (71.3%) for ulnar nerve, 79 (98.7%) for tibial nerve and in 79 (98.7%) patients for peroneal nerve. Nerve-specific motor nerve conduction study (MNCS) abnormality was found in 47 (58.8%) for median nerve, 43/80 (53.8%) for ulnar nerve, 59 (73.7%) for tibial nerve and in 57(71.3%) patients for peroneal nerve. Nerve-specific sensory nerve conduction study (SNCS) abnormality was present in 43 (53.3%) for median nerve, 43 (53.3%) for ulnar nerve, 50 (62.5%) for sural nerve, and in 49 (61.3%) patients for superficial peroneal nerve. Overall rate of abnormality was 85% for F-wave minimal latencies in comparison with 64% for MNCS and 56% for SNCS. Conclusion: Minimal F-wave latency can be an effective diagnostic parameter for detection of polyneuropathy. This can facilitate in early detection and management of polyneuropathy.

A patient treated with ofatumumab for myasthenia gravis in conjunction with systemic lupus erythematosus and thyroid carcinoma.

Myasthenia gravis (MG) is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. Anti-CD20 monoclonal antibodies, such as ofatumumab demonstrated promising disease control in MG patients. We presented the rare case of a 34-year-old female with acetylcholine receptor-positive myasthenia gravis (AChR-MG), concomitant with systemic lupus erythematosus (SLE) and metastatic thyroid carcinoma, who was treated with ofatumumab and exhibited improvements during follow-up.

Body Composition, Sarcopenia, and Serum Myokines in Acromegaly: A Narrative Review.

Patients with active acromegaly have a higher percentage of lean body mass, a lower percentage of fat body mass, and an increase in their extracellular water compartment compared to healthy individuals. However, muscle function appears to be compromised in patients with acromegaly, with some experiencing worsened physical performance and sarcopenia. Myokine alterations, insulin resistance, dysregulation of protein metabolism, muscle oxidative stress, neuromuscular junction impairment, and increased ectopic intramuscular fat deposits may play roles in muscle dysfunction in patients with acromegaly.

Deficiency in transmitter release triggers homeostatic transcriptional changes that increase presynaptic excitability.

Weakening of synaptic transmission at the Drosophila larval neuromuscular junction triggers two forms of homeostatic compensation, one that increases the probability of glutamate release per action potential (Pr) and another that increases motoneuron (MN) activity. We investigated the molecular changes in MNs that underlie the increase in MN activity. RNA-seq analysis on MNs whose glutamate release is weakened by knockdown of components of the MN transmitter release machinery reveals a reduction in expression of a group of genes that encode potassium channels and their positive modulators. These results identify a mechanism of compensation for weakened synaptic transmission by MNs, which engages a transcriptional program in those cells to increase firing and, thereby, ensure sufficient locomotory drive.

Circ_0076490 silencing inhibits MAPK1 expression to decrease the proliferation and increase apoptosis of Jurkat cells by regulating miR-144-3p in myasthenia gravis

ABSTRACT Background Myasthenia gravis (MG) is a both neuromuscular junction and antibody-mediated autoimmune disease, and its pathogenesis involves the regulation of circular RNAs (circRNAs). However, the role of circ_0076490 in MG and the underlying mechanism remain unknown. Methods RNA levels of circ_0076490, microRNA-144-3p (miR-144-3p), and mitogen-activated protein kinase 1 (MAPK1) were detected by quantitative real-time polymerase chain reaction. Cell viability and proliferation were investigated by cell counting kit-8 and 5-Ethynyl-29-deoxyuridine assays, respectively. Cell cycle and apoptosis were assessed by flow cytometry analysis. The putative binding relationship of miR-144-3p and circ_0076490 or MAPK1 was predicted by circular RNA interactome and TargetScan online databases, respectively, and identified through dual-luciferase reporter assay and RNA pull-down assay. Results We observed dramatic increases of circ_0076490 and MAPK1 expression and a decrease of miR-144-3p expression in the peripheral blood of MG patients in comparison with healthy controls. Reduced expression of circ_0076490 induced an inhibitory effect on the proliferation of Jurkat cells and a promoting effect on cell apoptosis. Additionally, miR-144-3p was identified as a target miRNA of circ_0076490, and its depletion attenuated circ_0076490 knockdown-mediated effects on the proliferation and apoptosis of Jurkat cells. MAPK1 was a target gene of miR-144-3p and its overexpression rescued decreased cell proliferation and increased cell apoptosis induced by miR-144-3p introduction. Furthermore, circ_0076490 regulated MAPK1 expression by interacting with miR-144-3p. Conclusion Circ_0076490 knockdown inhibited proliferation and induced apoptosis of Jurkat cells through the regulation of the miR-144-3p/MAPK1 axis, providing potential targets for developing improved therapy of MG.

Vitamin D deficiency and risk of myasthenia gravis

Background: An autoimmune condition known as myasthenia gravis (MG) targets the receptors for neurotransmitter acetylcholine at the neuromuscular junction, resulting in inhibition of muscle contraction. This results in muscle weakness resulting in a decrease in quality of life. Immunoregulation and muscle contractility are known to play a role in vitamin D. Literature on how vitamin D affects myasthenia gravis risk has not been widely carried out and the results are still controversial.Objective: To evaluate the association between vitamin D and MG risk.Methods: The search of the literature was conducted from PubMed, Cochrane Library, Embase, and EBSCOhost with the eligibility criteria determined by the authors. The literature search was using MeSH Term, text word, and title/abstract.Results: Two articles were selected and critically appraised. The first article shows an odds ratio of 3.96 (CI95 1.26 to 12.52), which means that myasthenia gravis has vitamin D levels almost 4 times lower than healthy population. A case-control study that followed described a comparison of mean levels of vitamin D (25(OH)D) in myasthenia gravis (mean, 18.8±8.4 ng/mL) compared to healthy controls (26.3±6.1). ng/mL) (p &lt;0.05). Both studies revealed a strong interaction between MG and vitamin D inadequacy. Conclusion: Both studies above support the theory that vitamin D deficiency is associated with the risk of developing MG.

Can non-invasive motor unit analysis reveal distinct neural strategies of force production in young with uncomplicated type 1 diabetes?

to investigate the early consequences of type 1 diabetes (T1D) on the neural strategies of muscle force production. motor unit (MU) activity was recorded from the vastus lateralis muscle with High-Density surface Electromyography during isometric knee extension at 20 and 40% of maximum voluntary contraction (MVC) in 8 T1D (4 males, 4 females, 30.5 ± 3.6years) and 8 matched control (4 males, 4 females, 27.3 ± 5.9years) participants. Muscle biopsies were also collected from vastus lateralis for fiber type analysis, including myosin heavy chain (MyHC) isoform content via protein and mRNA expression. MVC was comparable between groups as well as MU conduction velocity, action potentials' amplitude and proportions of MyHC protein isoforms. Nonetheless, MU discharge rate, relative derecruitment thresholds and mRNA expression of MyHC isoform I were lower in T1D. young people with uncomplicated T1D present a different neural control of muscle force production. Furthermore, differences are detectable non-invasively in absence of any functional manifestation (i.e., force production and fiber type distribution). These novel findings suggest that T1D has early consequences on the neuromuscular system and highlights the necessity of a better characterization of neural control in this population.

Transplantation of embryonic spinal motor neurons into peripheral nerves enables functional reconstruction of a denervated diaphragm

Respiratory muscle paralysis due to trauma or neurodegenerative diseases can have devastating consequences. Only a few studies have investigated the reconstruction of motor function in denervated diaphragms caused by such conditions. Here, we studied the efficacy of transplanting E14 embryonic spinal motor neurons (SMNs) into peripheral nerve grafts for functionally reconstructing a denervated diaphragm in a rat model. The diaphragms of 8-week-old male Fischer 344 rats were first denervated by transecting the phrenic nerves. Subsequently, peripheral nerve grafts taken from the lower limb were used for neurotization of the denervated diaphragms. One week later, fetal E14 SMNs were transplanted into the peripheral nerve grafts. After 3 months, we observed functional contraction of the diaphragm following neuromuscular electrical stimulation (NMES) of the peripheral nerve graft. Additionally, we confirmed that SMN transplantation into the peripheral nerve graft had an inhibitory effect on diaphragm muscle atrophy. The SMNs transplanted into the peripheral nerve grafts formed a structure similar to the spinal cord, and the neuromuscular junction of the denervated diaphragm was reinnervated. These findings suggest the establishment of an ectopic motor neuron pool in the peripheral nerve graft. Free peripheral intra-nerve SMN transplantation in combination with NMES, which can be applied for diaphragmatic pacing, offers novel insights into the development of neuroregenerative therapies for treating life-threatening and intractable respiratory muscle paralysis caused by severe nerve damage and degenerative diseases.

Dystroglycan-HSPG interactions provide synaptic plasticity and specificity.

This study examined the roles of the laminin and proteoglycan receptor dystroglycan (DG) in extracellular matrix stabilization and cellular mechanosensory processes conveyed through communication between the extracellular matrix (ECM) and cytoskeleton facilitated by DG. Specific functional attributes of HS-proteoglycans (HSPGs) are conveyed through interactions with DG and provide synaptic specificity through diverse interactions with an extensive range of cell attachment and adaptor proteins which convey synaptic plasticity. HSPG-DG interactions are important in phototransduction and neurotransduction and facilitate retinal bipolar-photoreceptor neuronal signaling in vision. Besides synaptic stabilization, HSPG-DG interactions also stabilize basement membranes and the ECM and have specific roles in the assembly and function of the neuromuscular junction. This provides neuromuscular control of muscle systems that control conscious body movement as well as essential autonomic control of diaphragm, intercostal and abdominal muscles and muscle systems in the face, mouth and pharynx which assist in breathing processes. DG is thus a multifunctional cell regulatory glycoprotein receptor and regulates a diverse range of biological and physiological processes throughout the human body. The unique glycosylation of the αDG domain is responsible for its diverse interactions with ECM components in cell-ECM signaling. Cytoskeletal cell regulatory switches assembled by the βDG domain in its role as a nuclear scaffolding protein respond to such ECM cues to regulate cellular behavior and tissue homeostasis thus DG has fascinating and diverse roles in health and disease.

Inducible deletion of endothelial cell Efnb2 delays capillary regeneration and attenuates myofibre reinnervation following myotoxin injury in mice.

Acute injury of skeletal muscle disrupts myofibres, microvessels and motor innervation. Myofibre regeneration is well characterized, however its relationship with the regeneration of microvessels and motor nerves is undefined. Endothelial cell (EC) ephrin-B2 (Efnb2) is required for angiogenesis during embryonic development and promotes neurovascular regeneration in the adult. We hypothesized that, following acute injury to skeletal muscle, loss of EC Efnb2 would impair microvascular regeneration and the recovery of neuromuscular junction (NMJ) integrity. Mice (aged 3-6months) were bred for EC-specific conditional knockout (CKO) of Efnb2 following tamoxifen injection with non-injected CKO mice as controls (CON). The gluteus maximus, tibialis anterior or extensor digitorum longus muscle was then injured with local injection of BaCl2. Intravascular staining with wheat germ agglutinin revealed diminished capillary area in the gluteus maximus of CKO vs. CON at 5days post-injury (dpi); both recovered to uninjured (0dpi) level by 10dpi. At 0dpi, tibialis anterior isometric force of CKO was less than CON. At 10dpi, isometric force was reduced by half in both groups. During intermittent contractions (75Hz, 330mss-1, 120s), isometric force fell during indirect (sciatic nerve) stimulation whereas force was maintained during direct (electrical field) stimulation of myofibres. Neuromuscular transmission failure correlated with perturbed presynaptic (terminal Schwann cells) and postsynaptic (nicotinic acetylcholine receptors) NMJ morphology in CKO. Resident satellite cell number on extensor digitorum longus myofibres did not differ between groups. Following acute injury of skeletal muscle, loss of Efnb2 in ECs delays capillary regeneration and attenuates recovery of NMJ structure and function. KEY POINTS: The relationship between microvascular regeneration and motor nerve regeneration following skeletal muscle injury is undefined. Expression of Efnb2 in endothelial cells (ECs) is essential to vascular development and promotes neurovascular regeneration in the adult. To test the hypothesis that EfnB2 in ECs is required for microvascular regeneration and myofibre reinnervation, we induced conditional knockout of Efnb2 in ECs of mice. Acute injury was then induced by BaCl2 injection into gluteus maximus, tibialis anterior or extensor digitorum longus (EDL) muscle. Capillary regeneration was reduced at 5days post-injury (dpi) in gluteus maximus of conditional knockout vs. controls; at 10dpi, neither differed from uninjured. Nerve stimulation revealed neuromuscular transmission failure in tibialis anterior with perturbed neuromuscular junction structure. Resident satellite cell number on EDL myofibres did not differ between groups. Conditional knockout of EC Efnb2 delays capillary regeneration and attenuates recovery of neuromuscular junction structure and function.

The Injected Plasma of Myasthenia Gravis Patient with A Low T-reg Level Caused Clinical Myasthenic Syndromes in Swiss-Webster Mice

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease affecting neuromuscular junction involvement. The finding that T-reg level in MG patients was lower than that in normal persons leads to the idea that the primary pathology of the disease is T-reg dependent. The T-reg level of MG patients seems to be decreasing compared to that of normal persons. The study was conducted to observe the contribution of T-reg level in plasma injected into Swiss-Webster mice to develop clinically and pathologically myasthenic syndromes.METHODS: Swiss-Webster mice were grouped into three groups: the groups received plasma with normal, low, and high T-reg levels, respectively. The T-reg levels of the mice were measured with flow cytometry analysis and a human regulatory T-cell cocktail for T-cell surface cell marker. The motor function, interleukin (IL)-2, interferon (IFN)-γ, and thymus weight of mice were measured after the injection. Histopathological examination was performed to analyze mice’s muscles and thymus.RESULTS: The result identified that the motor function (2-week treatment group: p=0.021 and 3-week treatment group: p=0.032) and muscle width (p=0.014, p=0.032 and p≤0.001) were significantly lower in the low T-reg level plasma group compared to control and high T-reg level plasma groups. The thymus showed an increase in weight without an increase in the cortex-medulla ratio of the thymus, indicating hyperplasia. Both IL-2 and IFN-γ levels were lower in the low and high T-reg level groups compared with the control group, indicating the autoimmune process.CONCLUSION: Low T-reg level was associated with lower motor function, muscle width, increased thymus weight, as well as lower IL-2 and IFN-γ levels. T-reg level contributed to clinical myasthenic syndromes but not pathological findings. This research method is expected to be a basis for the development of animal models with Swiss-Webster mice.KEYWORDS: animal model, Myasthenia gravis, Swiss-Webster mice

Targeted Treatments for Myasthenia Gravis in Children and Adolescents.

Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction affecting children and adults. MG is a treatable condition with most patients requiring immunosuppression for disease control and/or remission. Juvenile myasthenia gravis (JMG) is rare in comparison with adult-onset MG but given the same underlying pathophysiology, treatment strategies are similar to those in adults. Until recently, there were only a few randomised controlled trials (RCTs) for MG treatments in adults and none in children, and management strategies were primarily based on expert consensus. In addition, treatment options for refractory MG cases have been severely limited, resulting in poor long-term quality of life in such patients due to the significant disease burden. Recently, there have been several RCTs focussing on novel therapeutic strategies with potentially promising outcomes, suggesting a change in MG management over the coming years and access to more effective and faster-acting drugs for MG patients. This paper will review current and new MG treatments including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, with a focus on juvenile myasthenia gravis.

HnRNP R promotes O-GlcNAcylation of eIF4G and facilitates axonal protein synthesis

Motoneurons critically depend on precise spatial and temporal control of translation for axon growth and the establishment and maintenance of neuromuscular connections. While defects in local translation have been implicated in the pathogenesis of motoneuron disorders, little is known about the mechanisms regulating axonal protein synthesis. Here, we report that motoneurons derived from Hnrnpr knockout mice show reduced axon growth accompanied by lowered synthesis of cytoskeletal and synaptic components in axons. Mutant mice display denervated neuromuscular junctions and impaired motor behavior. In axons, hnRNP R is a component of translation initiation complexes and, through interaction with O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt), modulates O-GlcNAcylation of eIF4G. Restoring axonal O-GlcNAc levels rescued local protein synthesis and axon growth defects of hnRNP R knockout motoneurons. Together, these findings demonstrate a function of hnRNP R in controlling the local production of key factors required for axon growth and formation of neuromuscular innervations.