Social anxiety disorder-associated gut microbiota increases social fear.

Social anxiety disorder (SAD) is a crippling psychiatric disorder characterized by intense fear or anxiety in social situations and their avoidance. However, the underlying biology of SAD is unclear and better treatments are needed. Recently, the gut microbiota has emerged as a key regulator of both brain and behaviour, especially those related to social function. Moreover, increasing data supports a role for immune function and oxytocin signalling in social responses. To investigate whether the gut microbiota plays a causal role in modulating behaviours relevant to SAD, we transplanted the microbiota from SAD patients, which was identified by 16S rRNA sequencing to be of a differential composition compared to healthy controls, to mice. Although the mice that received the SAD microbiota had normal behaviours across a battery of tests designed to assess depression and general anxiety-like behaviours, they had a specific heightened sensitivity to social fear, a model of SAD. This distinct heightened social fear response was coupled with changes in central and peripheral immune function and oxytocin expression in the bed nucleus of the stria terminalis. This work demonstrates an interkingdom basis for social fear responses and posits the microbiome as a potential therapeutic target for SAD.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.

The gut microbiota alone and in combination with a social stimulus regulates cocaine reward in the mouse.

The gut microbiota is a key factor in the maintenance of physiological homeostasis and immunity. Correlational studies have demonstrated that alterations in microbiota composition have been associated with addiction. Moreover, animal studies have confirmed a link between reward and social processes, which may be shaped by the gut microbiota thus influencing neurodevelopment and the programming of social behaviors across diverse animal species. However, whether there is an interaction between the microbiota and social reward processes in the context of drug reward remains unclear. To this end, we explored the influence of gut microbiota in regulating behaviourally conditioned responses to different rewards (cocaine and social interactions). Depletion of the intestinal microbiota resulted in differential reward responses to both drug and social stimuli with an attenuation of the former and enhancement of the latter independent of concomitant immune changes. Moreover, the combination of depleting the gut microbiota in the presence of a positive social stimulus attenuates cocaine reward. Together these data suggest that the two-pronged approach of targeting the microbiota and enhancing social behaviour could constitute a valuable component in reducing harm in drug use by altering the salient effects of cocaine.

The evolution of the axonal transport toolkit.

Neurons are highly polarized cells that critically depend on long-range, bidirectional transport between the cell body and synapse for their function. This continual and highly coordinated trafficking process, which takes place via the axon, has fascinated researchers since the early 20th century. Ramon y Cajal first proposed the existence of axonal trafficking of biological material after observing that dissociation of the axon from the cell body led to neuronal degeneration. Since these first indirect observations, the field has come a long way in its understanding of this fundamental process. However, these advances in our knowledge have been aided by breakthroughs in other scientific disciplines, as well as the parallel development of novel tools, techniques and model systems. In this review, we summarize the evolution of tools used to study axonal transport and discuss how their deployment has refined our understanding of this process. We also highlight innovative tools currently being developed and how their addition to the available axonal transport toolkit might help to address key outstanding questions.

PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors.

Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the years, including the formation, endocytosis and trafficking of signalling-competent ligand-receptor complexes. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors are still elusive. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of brain-derived neurotrophic factor (BDNF)-activated TrkB (also known as NTRK2) and p75NTR (also known as NGFR) in motor neurons. Here, using a proteomics approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1-knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors.

Dissection, in vivo imaging and analysis of the mouse epitrochleoanconeus muscle.

Analysis of rodent muscles affords an opportunity to glean key insights into neuromuscular development and the detrimental impact of disease-causing genetic mutations. Muscles of the distal leg, for instance the gastrocnemius and tibialis anterior, are commonly used in such studies with mice and rats. However, thin and flat muscles, which can be dissected, processed and imaged without major disruption to muscle fibres and nerve-muscle contacts, are more suitable for accurate and detailed analyses of the peripheral motor nervous system. One such wholemount muscle is the predominantly fast twitch epitrochleoanconeus (ETA), which is located in the upper forelimb, innervated by the radial nerve, and contains relatively large and uniformly flat neuromuscular junctions (NMJs). To facilitate incorporation of the ETA into the experimental toolkit of the neuromuscular disease field, here, we describe a simple method for its rapid isolation (<5 min), supported by high-resolution videos and step-by-step images. Furthermore, we outline how the ETA can be imaged in live, anaesthetised mice, to enable examination of dynamic cellular processes occurring at the NMJ and within intramuscular axons, including transport of organelles, such as mitochondria and signalling endosomes. Finally, we present reference data on wild-type ETA fibre-type composition in young adult, male C57BL6/J mice. Comparative neuroanatomical studies of different muscles in rodent models of disease can generate critical insights into pathogenesis and pathology; dissection of the wholemount ETA provides the possibility to diversify the repertoire of muscles analysed for this endeavour.

The live biotherapeutic Blautia stercoris MRx0006 attenuates social deficits, repetitive behaviour, and anxiety-like behaviour in a mouse model relevant to autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social behaviour, increased repetitive behaviour, anxiety and gastrointestinal symptoms. The aetiology of ASD is complex and involves an interplay of genetic and environmental factors. Emerging pre-clinical and clinical studies have documented a potential role for the gut microbiome in ASD, and consequently, the microbiota represents a potential target in the development of novel therapeutics for this neurodevelopmental disorder. In this study, we investigate the efficacy of the live biotherapeutic strain, Blautia stercoris MRx0006, in attenuating some of the behavioural deficits in the autism-relevant, genetic mouse model, BTBR T+ Itpr3tf/J (BTBR). We demonstrate that daily oral administration with MRx0006 attenuates social deficits while also decreasing repetitive and anxiety-like behaviour. MRx0006 administration increases the gene expression of oxytocin and its receptor in hypothalamic cells in vitro and increases the expression of hypothalamic arginine vasopressin and oxytocin mRNA in BTBR mice. Additionally at the microbiome level, we observed that MRx0006 administration decreases the abundance of Alistipes putredinis, and modulates the faecal microbial metabolite profile. This alteration in the metabolite profile possibly underlies the observed increase in expression of oxytocin, arginine vasopressin and its receptors, and the consequent improvements in behavioural outcomes. Taken together, these findings suggest that the live biotherapeutic MRx0006 may represent a viable and efficacious treatment option for the management of physiological and behavioural deficits associated with ASD.

Green Synthesis of Superparamagnetic Iron Oxide Nanoparticles with Eucalyptus globulus Extract and Their Application in the Removal of Heavy Metals from Agricultural Soil.

The green synthesis of metal oxide nanoparticles is presented as an excellent sustainable alternative for achieving nanostructures, with potential applications. This research provides important information regarding the influence of the type of solvent used in extracting organic reducing agents from E. globulus on the FeO NPs green synthesis protocol. A broad approach to characterization is presented, where UV-vis spectrophotometry suggests the presence of this type of nanoparticulate material. Likewise, the reduction mechanism was evaluated by FT-IR and the magnetic properties were evaluated by PPSM. In addition, characterizations were linked via elemental analysis (EDX), crystallographic characterization (XRD), electron microscopy (SEM/STEM), and Z potential to evaluate colloidal stability. The results show the influence of the type of solvent used for the extraction of organic reducing agents from E. globulus, and the effect on the synthesis of FeO NPs. In addition, the nanostructure material obtained showed excellent efficiency in the remediation of agricultural soil, eliminating metals such as Cr-VI, Cd, and, to a lesser extent, Pb.

ZnO Nanoparticles Obtained by Green Synthesis as an Alternative to Improve the Germination Characteristics of L. esculentum.

Tomato is an important crop due to its nutritional contributions and organoleptic properties, which make it an appetizing vegetable around the world. In its sowing, the use of seed is the most accessible propagation mechanism for farmers. However, the induction to germination and emergence is often limited in the absence of stimulants that promote the development and growth of the seedling, added to the interference of infectious agents that notoriously reduce the vitality and viability of the seed. Given this, it was proposed as a research objective to determine the effect of zinc oxide nanoparticles (ZnO NPs) mediated by a green route on the germinative characteristics of Lycopersicon esculentum Mill. 1768 "tomato". The experimental phase consisted of the synthesis of ZnO NPs and its subsequent characterization. After its synthesis, its inoculation was conducted during the germination of seeds of L. esculentum, considering six sample groups for the treatment with zinc nanoparticles (T1: Control; T2: 21.31 ppm; T3: 33.58 ppm; T4: 49.15 ppm; T5: 63.59 and T6: 99.076 ppm). The results indicate that concentrations close to 100 ppm of ZnO NPs are ideal in the treatment of L. esculentum seeds, due to the promotion of enzymatic and metabolic activity to achieve cell elongation; likewise, the biosynthesized nanoparticles showed no phytotoxicity, due to the fact that, in all the treatments, there were processes of germination and emergence. This was linked to the generation of a Zn0-phenolate complex through a chelating effect, which generates compatibility with the seed and, compared to classic inorganic synthesis, usually shows phytotoxicity. In this sense, green synthesis is presented as a great alternative in this type of application.

Influence of the Alcoholic/Ethanolic Extract of Mangifera indica Residues on the Green Synthesis of FeO Nanoparticles and Their Application for the Remediation of Agricultural Soils.

The green synthesis of iron oxide nanoparticles (FeO NP) has been investigated using the extract in absolute ethanolic and alcoholic solvents 96% from the peel of the mango fruit (Mangifera indica), thus evaluating the influence of the type of solvent on the extraction of reducing metabolites. A broad approach to characterization initially controlled by UV-vis spectrophotometry has been directed, the formation mechanism was evaluated by Fourier transform infrared spectroscopy (FTIR), the magnetic properties by characterization by Physical Property Measurement System (PPSM), in addition to a large number of techniques such as X-ray energy dispersive spectroscopy (EDS), X-ray diffraction (DRX), transmission electron microscopy (TEM/STEM), electron energy loss spectroscopy (EELS), and Z potential to confirm the formation of FeO NP. The results suggest better characteristics for FeO NP synthesized using 96% alcoholic solvent extract. The successful synthesis was directly proven in the removal of metals (Cr-VI, Cd, and Pb) as a potential alternative in the remediation of agricultural soils.

Evaluation of phenolic antioxidant-linked in vitro bioactivity of Peruvian corn (Zea mays L.) diversity targeting for potential management of hyperglycemia and obesity.

Peruvian corn biodiversity is one of the highest in the world and may represent an important natural source of health relevant phenolic bioactive compounds whose potential needs to be investigated. This study investigated twenty-two Peruvian corn samples corresponding to five corn races (Arequipeño, Cabanita, Kculli, Granada and Coruca) in relation to their total phenolic contents (TPC), anthocyanin contents, Ultra-Performance Liquid Chromatography (UPLC) phenolic profiles and antioxidant capacity (ABTS and ORAC methods). Subsequently using both free and cell-wall bound phenolic fractions their health relevance targeting hyperglycemia (α-glucosidase and α-amylase inhibition) and obesity (lipase inhibition) potentials was evaluated using in vitro assay models. Antioxidant capacity and TPC were high in bound fractions from yellow-colored races in contrast to the purple-colored race (Kculli) which had high TPC (mainly anthocyanins) and antioxidant capacity in the free form. The major phenolic acids detected by UPLC were ferulic and p-coumaric acids. High α-glucosidase (32.5-76.1%, 25 mg sample dose) and moderate α-amylase inhibitory activities (13.6-29.0%, 250 mg sample dose) were found in all free fractions, but only samples from the Kculli race had lipase inhibitory activity (58.45-92.16%, 12.5 mg sample dose). Principal component analysis revealed that the variability of data was affected by the race and the α-glucosidase and lipase inhibitory activities positively correlated with anthocyanins and antioxidant capacity. Some accessions of Kculli, Granada and Cabanita races are promising for future breeding strategies focused on the development of improved corn varieties targeted for the design of functional foods relevant for hyperglycemia and obesity prevention.

[Intravenous radioiodine and recombinant human TSH in a patient with extensive thyroid cáncer. Report of one case]. / Tratamiento con radioyodo endovenoso y estimulación con TSH recombinante humana en paciente con cáncer de tiroides extenso. Caso clínico.

We report a 72-years-old male patient with extensive differentiated thyroid cancer (DTC), who required a tracheostomy and gastrostomy. Considering his clinical condition, risk of aspiration and management of the ostomies, radioiodine (131I) was administered intravenously, using recombinant human thyrotropin (rhTSH) and levothyroxine. The procedure was successful, both clinically and in terms of radioprotection.

A microbial signature for Crohn's disease.

OBJECTIVE: A decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study. DESIGN: We analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences. RESULTS: In the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively. CONCLUSIONS: Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions.

Rab35 Functions in Axon Elongation Are Regulated by P53-Related Protein Kinase in a Mechanism That Involves Rab35 Protein Degradation and the Microtubule-Associated Protein 1B.

UNLABELLED: Rab35 is a key protein for cargo loading in the recycling endosome. In neuronal immortalized cells, Rab35 promotes neurite differentiation. Here we describe that Rab35 favors axon elongation in rat primary neurons in an activity-dependent manner. In addition, we show that the p53-related protein kinase (PRPK) negatively regulates axonal elongation by reducing Rab35 protein levels through the ubiquitin-proteasome degradation pathway. PRPK-induced Rab35 degradation is regulated by its interaction with microtubule-associated protein 1B (MAP1B), a microtubule stabilizing binding protein essential for axon elongation. Consistently, axon defects found in MAP1B knock-out neurons were reversed by Rab35 overexpression or PRPK inactivation suggesting an epistatic relationship among these proteins. These results define a novel mechanism to support axonal elongation, by which MAP1B prevents PRPK-induced Rab35 degradation. Such a mechanism allows Rab35-mediated axonal elongation and connects the regulation of actin dynamics with membrane trafficking. In addition, our study reveals for the first time that the ubiquitin-proteasome degradation pathway regulates a Rab GTPase. SIGNIFICANCE STATEMENT: Rab35 is required for axonal outgrowth. We define that its protein levels are negatively regulated by p53-related protein kinase (PRPK). We show that microtubule-associated protein 1B (MAP1B) interacts with PRPK, preventing PRPK-dependent Rab35 proteasome degradation. We demonstrate that Rab35 regulates Cdc42 activity in neurons. This is the first evidence showing that a Rab protein is regulated by degradation dependent on the ubiquitin-proteasome system.

Rab-mediated trafficking role in neurite formation.

Neuronal cells are characterized by the presence of two confined domains, which are different in their cellular properties, biochemical functions and molecular identity. The generation of asymmetric domains in neurons should logically require specialized membrane trafficking to both promote neurite outgrowth and differential distribution of components. Members of the Rab family of small GTPases are key regulators of membrane trafficking involved in transport, tethering and docking of vesicles through their effectors. RabGTPases activity is coupled to the activity of guanine nucleotide exchange factors or GEFs, and GTPase-activating proteins known as GAPs. Since the overall spatiotemporal distribution of GEFs, GAPs and Rabs governs trafficking through the secretory and endocytic pathways, affecting exocytosis, endocytosis and endosome recycling, it is likely that RabGTPases could have a major role in neurite outgrowth, elongation and polarization. In this review we summarize the evidence linking the functions of several RabGTPases to axonal and dendritic development in primary neurons, as well as neurite formation in neuronal cell lines. We focused on the role of RabGTPases from the trans-Golgi network, early/late and recycling endosomes, as well as the function of some Rab effectors in neuritogenesis. Finally, we also discuss the participation of the ADP-ribosylation factor 6, a member of the ArfGTPase family, in neurite formation since it seems to have an important cross-talk with RabGTPases.

BeCAS: biomedical concept recognition services and visualization.

SUMMARY: The continuous growth of the biomedical scientific literature has been motivating the development of text-mining tools able to efficiently process all this information. Although numerous domain-specific solutions are available, there is no web-based concept-recognition system that combines the ability to select multiple concept types to annotate, to reference external databases and to automatically annotate nested and intercepted concepts. BeCAS, the Biomedical Concept Annotation System, is an API for biomedical concept identification and a web-based tool that addresses these limitations. MEDLINE abstracts or free text can be annotated directly in the web interface, where identified concepts are enriched with links to reference databases. Using its customizable widget, it can also be used to augment external web pages with concept highlighting features. Furthermore, all text-processing and annotation features are made available through an HTTP REST API, allowing integration in any text-processing pipeline. AVAILABILITY: BeCAS is freely available for non-commercial use at http://bioinformatics.ua.pt/becas. CONTACTS: tiago.nunes@ua.pt or jlo@ua.pt.

Ethical Concerns about Fashionable Dog Breeding.

The historical relationship between humans and dogs has involved selective breeding for various purposes, such as hunting, guarding, and service roles. However, over time, there has been a shift in preferences from functionality to aesthetics, which has influenced the diverse sizes, shapes, and coats of dog breeds. This review looks at fashionable dog breeding and questions the ethics of prioritising looks over health and behaviour. It aims to alert potential owners, breeders, and regulators to the importance of considering a dog's overall well-being, not just its appearance, which has resulted in fad breeding, leading to genetic disorders, health issues, and a loss of biodiversity. Ethical concerns arise from breeding brachycephalic breeds with respiratory conditions, inbreeding causing inherited disorders, and overbreeding popular breeds while shelter dogs remain unadopted. Additionally, the impact of cosmetic surgeries on popular dog breeds, as well as the neglect of behavioural traits in favour of physical characteristics and strict breeding practices are also considered. The current breeding model can have a negative impact on the emotional and cognitive well-being of dogs, resulting in issues such as aggression, anxiety, and other behavioural problems that can significantly reduce their overall quality of life. Unregulated breeding practices and the demand for rare breeds can lead to illegal breeding, compromising animal welfare. Prospective owners, veterinarians, kennel clubs, and legislators all need to play a responsible role in protecting animals.

Enhanced antimicrobial efficacy of biogenic ZnO nanoparticles through UV-B activation: A novel approach for textile garment.

Zinc oxide nanoparticles (ZnO NP) are characterized by novel properties which have been attracting the attention of different lines of research due to their wide applicability. Obtaining this nanomaterial is strongly linked to biogenic synthesis methods, which have also been developed in this research, using Coriandrum sativum extract as a reducing agent. ZnO NPs have been properly characterized by techniques to evaluate their morphology by transmission electron microscopy (TEM) and elemental analysis by EDX. The evaluation of the antimicrobial and antifungal effects is linked to the use of a system provided by "locker sanitizer" equipment, which has been designed and built as part of this research, and is intended to treat textile garments by nebulizing the ZnO NP colloid (99.08 µg/mL) + UV-B, water + UV-B, and UV-B only, and also to evaluate the influence of the treatment time for 1, 2 and 3 min. In this sense, it is known that the nanomaterial used shows a better response to UV light because more hydroxyl radicals are produced, leading to a higher reaction rate, which results in greater efficiency in inhibitory processes. The results show that the use of the locker sanitizer is more efficient when using ZnO NP + UV-B light since it achieved 100 % growth inhibition against E. coli, C. albicans, and A. brasiliensis, and >99 % against S. aureus, after 3 min of treatment.

Dendritic voltage imaging maps the biophysical basis of plateau potentials in the hippocampus.

Dendrites on neurons integrate synaptic inputs to determine spike timing. Dendrites also convey back-propagating action potentials (bAPs) which interact with synaptic inputs to produce plateau potentials and to mediate synaptic plasticity. The biophysical rules which govern the timing, spatial structures, and ionic character of dendritic excitations are not well understood. We developed molecular, optical, and computational tools to map sub-millisecond voltage dynamics throughout the dendritic trees of CA1 pyramidal neurons under diverse optogenetic and synaptic stimulus patterns, in acute brain slices. We observed history-dependent bAP propagation in distal dendrites, driven by locally generated Na + spikes (dSpikes). Dendritic depolarization creates a transient window for dSpike propagation, opened by A-type K V channel inactivation, and closed by slow Na V inactivation. Collisions of dSpikes with synaptic inputs triggered calcium channel and N-methyl-D-aspartate receptor (NMDAR)-dependent plateau potentials, with accompanying complex spikes at the soma. This hierarchical ion channel network acts as a spike-rate accelerometer, providing an intuitive picture of how dendritic excitations shape associative plasticity rules.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.