Neuromuscular Research Articles

Child Neurology: Severe GMPPB-Related Congenital Muscular Dystrophy With Rapidly Progressive Encephalopathy Leading to Infantile Death.

Pathogenic variants in GMPPB cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.624T>G and c.1000G>A) in GMPPB who presented acutely in status epilepticus progressing to refractory hemodynamic instability and multiorgan failure leading to death 20 days after admission. Brain MRI showed a pattern of symmetric diffusion restriction consistent with possible vigabatrin toxicity and progressive cerebral volume loss. Postmortem neuropathology examination confirmed features of dystroglycanopathy including patchy loss of dystroglycan staining of muscle. This report of infantile death in an individual with a GMPPB-related disorder raises concern for potential risk of early mortality possibly exacerbated by vigabatrin toxicity.

Effects of GDF6 on active protein synthesis by cells of degenerated intervertebral disc.

Intervertebral disc degeneration (IVD) is a leading cause of low back pain, a prevalent musculoskeletal condition. IVD degeneration is characterized by the degradation of nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates (EP). Growth Differentiation Factor 6 (GDF6), part of the bone morphogenetic protein family, has demonstrated potential in maintaining disc integrity. However, its precise role in cellular protein synthesis during IVD degeneration remains unclear. This study employed Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) to investigate the effects of GDF6 on protein synthesis in NP, AF, and EP cells isolated from degenerated human IVDs. Cells were cultured in SILAC media with and without GDF6 treatment. The proteomic profiles were analyzed via mass spectrometry, comparing newly synthesized "heavy" proteins with pre-existing "light" proteins. GDF6 treatment altered protein synthesis in degenerated IVD cells. In NP cells, GDF6 reduced the synthesis of matrisome proteins, including collagens and proteoglycans, while promoting proteins associated with ECM stability, such as LOX, PCOLCE and HAPLN1/3. AF cells demonstrated an upregulation of ECM-stabilizing proteins like POSTN and FMOD. EP cells showed minimal changes, but GDF6 enhanced the synthesis of collagen type II, suggesting improved ECM integrity. Secretome analysis revealed that GDF6 modulated extracellular signalling by promoting ECM-stabilizing proteins and reducing inflammatory markers. GDF6 exerts compartment-specific effects on protein synthesis in degenerated IVDs, promoting ECM stability, reducing fibrosis, and potentially preserving hydration. These findings support the potential of GDF6 as a therapeutic agent in treating IVD degeneration, particularly in NP-targeted therapies. Future studies should optimize GDF6 dosing and delivery to maximize its regenerative potential.

Live Imaging of Synaptic Vesicle Recycling in the Neuromuscular Junction of Dissected Larval Zebrafish

Live Imaging of Synaptic Vesicle Recycling in the Neuromuscular Junction of Dissected Larval Zebrafish

ISSLS Prize in Clinical Science 2025: Cartilage End Plate Defects Precede and Initiate Bony End Plate Defects and Disc Degeneration- An 'Integrated Total End Plate Score' Identify Preclinical Discs at Risk for Degeneration.

We utilized the Fast Low Angle Shot (FLASH) sequence to document the sequential changes in cartilaginous (CEP) and bony end plate (BEP) to study the influence on disc degeneration (DD). Routine MRI and FLASH sequences were used in 500 lumbar discs in 100 each of healthy volunteers (HV), low back pain patients treated conservatively (CG) and surgically (SG) to document CEP and BEP status, Pfirrmann Grade (PG) and various MRI parameters. The three groups were identical demographically but had a significantly different number of healthy discs (p < 0.01) and changes in CEP and BEP (p < 0.01), with patients having a higher severity of end plate changes and DD, even in asymptomatic discs. CEP abnormalities always appeared first, followed by a sequence of BEP defects of different severity, allowing the development of an 'Integrated Total End Plate Score' (I-TEPS). There was a good correlation between I-TEPS and PG, with a steep escalation of DD after a score of 7. A score of ≥ 7 was also associated with higher surgical incidence in patients with both degenerated and herniated discs. The most significant influencing factors for surgery was a combination of I-TEPS ≥ 7 with herniation (OR7.7;p-0.00), smoking (OR4.63;p-0.02), and an I-TEPS ≥ 7 (OR3.37;p-0.04). CEP changes identified by FLASH preceded BEP defects and DD. I-TEPS was superior to TEPS in identifying a subgroup of discs that had CEP abnormalities without BEP. An I-TEPS ≥ 7 had a significant correlation to the severity of DD, influenced variations in herniation and also surgical incidence.

The exocytosis regulator complexin controls spontaneous synaptic vesicle release in a CAPS-dependent manner at C. elegans excitatory synapses.

The balance between synaptic excitation and inhibition (E/I) is essential for coordinating motor behavior, yet the differential roles of exocytosis regulators in this balance are less understood. In this study, we investigated the roles of 2 conserved exocytosis regulators, complexin/CPX-1 and CAPS/UNC-31, in excitatory versus inhibitory synapses at Caenorhabditis elegans neuromuscular junctions. cpx-1 null mutants exhibited a marked increase in spontaneous release specifically at excitatory synapses, alongside an unequal reduction in excitatory and inhibitory evoked release. A clamping-specific knockin mutant, cpx-1(Δ12), which preserved evoked release, also showed a biased enhancement in excitatory spontaneous release. Conversely, the unc-31 null mutation, while maintaining normal spontaneous release, displayed a more pronounced reduction in evoked release at excitatory synapses. Notably, we found that CPX-1's clamping function is dependent on UNC-31 and is sensitive to external Ca2+. Pull-down experiments confirmed that CAPS/UNC-31 does not directly interact with complexin, implying an indirect regulatory mechanism. Moreover, complexin regulates activity-dependent synaptic plasticity, which is also UNC-31 dependent. The unexpected role of CAPS/UNC-31 in the absence of CPX-1 clamping function may underpin the synaptic E/I balance and coordinated behavioral outputs in different species.

α-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2+

α-Latrotoxin (αLTX) causes exhaustive release of neurotransmitters from nerve terminals in the absence of extracellular Ca2+ (Ca2+e). To investigate the mechanisms underlying this effect, we loaded mouse neuromuscular junctions with BAPTA-AM. This membrane-permeable Ca2+-chelator demonstrates that Ca2+e-independent effects of αLTX require an increase in cytosolic Ca2+ (Ca2+cyt). We also show that thapsigargin, which depletes Ca2+ stores, induces neurotransmitter release, but inhibits the effect of αLTX. We then studied αLTX’s effects on Ca2+cyt using neuroblastoma cells expressing signaling-capable or signaling-incapable variants of latrophilin-1, a G protein-coupled receptor of αLTX. Our results demonstrate that αLTX acts as a cation ionophore and a latrophilin agonist. In model cells at 0 Ca2+e, αLTX forms membrane pores and allows the influx of Na+; this reverses the Na+-Ca2+ exchanger, leading to the release of stored Ca2+ and inhibition of its extrusion. Concurrently, αLTX stimulates latrophilin signaling, which depletes a Ca2+ store and induces transient opening of Ca2+ channels in the plasmalemma that are sensitive to inhibitors of store-operated Ca2+ entry. These results indicate that Ca2+ release from intracellular stores and that Ca2+ influx through latrophilin-activated store-operated Ca2+ channels contributes to αLTX actions and may be involved in physiological control of neurotransmitter release at nerve terminals.

Contribution of Neuromuscular Junction Degradation to Muscle Decline in Burn Patients

Contribution of Neuromuscular Junction Degradation to Muscle Decline in Burn Patients

Experimental Study on Flexural Performance of Screw Clamping and Welding Joint for Prestressed Concrete Square Piles

To ensure the connection performance of precast concrete square piles, a screw clamping and welding joint connection is applied to the solid square piles. By conducting full-scale bending performance tests on six solid square pile specimens with cross-sectional side lengths of 300, 450, and 600 mm, including pile bodies, screw clamping joints, screw clamping, and welding joints, the bending load-bearing capacity, deformation capacity, and failure characteristics of the screw clamping–welding joint connection are compared and studied. The results show that the bending failure mode of the pile body specimens is shear failure in the flexural shear section and concrete crushing in the compression zone of the pure bending section; the bending failure mode of the screw clamping joint specimens are the pull-out of steel bar heads at the joint end plate; the bending failure mode of the screw clamping and welding joint specimens are concrete crushing in the compression zone of the pure bending section, steel bar breakage in the tension zone of the flexural shear section, and pull-out of steel bar heads at the end plate. It is worth noting that no significant damage occurred at the joints. The cracks in the pure bending section of the bending specimens mainly develop vertically and are evenly distributed, while some cracks in the flexural shear section develop obliquely towards the loading point, with branching. Compared to the pile body specimens, the cracking moment of the joint specimens is up to 16% higher, the ultimate moment is within 15% lower, and the maximum mid-span deflection is within 25% lower, indicating that the provision of anchorage reinforcement can increase the stiffness and cracking moment of the specimens.

Effect of sleep deprivation on gait complexity.

Gait complexity is considered an indicator of adaptability, reflecting the complex interaction between multiple components of the neuromuscular system. Previous research provided evidence that chronobiology, which reflects the individual expression of circadian rhythms, affects the regulation of gait dynamics. The literature also suggests the disruption of these circadian rhythms affects multiple human physiological systems. Considering the association between chronobiology and gait complexity, and its clinical relevance, it would be important to investigate whether the disruption of sleep-wake cycle could affect gait complexity. This study aimed to investigate the effect of 1 night of sleep deprivation on gait complexity and variability of healthy individuals, exploring potential implications for motor control. Seventeen healthy and young male adults underwent an in-lab supervised 24-hr sleep deprivation protocol, with gait complexity and variability assessed using detrended fluctuation analysis and coefficient of variation, respectively. Chronotype was also assessed through the Morningness-Eveningness Questionnaire. We observed a loss of gait complexity with sleep deprivation (PRE: 0.8 ± 0.13; POST24: 0.62 ± 0.08, p < 0.001), while gait variability remained unaltered (p = 0.132). Additionally, we demonstrated an association between gait complexity's relative changes and chronotype (r = -0.665, p = 0.004). Overall, our findings suggest sleep deprivation induces a decrease in the neuromuscular system's ability to flexibly adapt gait output. Moreover, we also highlight the importance of chronobiology in motor control, as we observed the more morning-type an individual is, the greater the loss of complexity following 1 night of sleep deprivation. Altogether, our findings underscore the potential impact of sleep deprivation on central processes underlying gait complexity.

Quality matters: chronic kidney disease progression is associated to reduced muscle strength independently of changes in skeletal muscle mass: an observational study

Abstract Background and hypothesis Chronic kidney disease (CKD) is commonly associated with multifactorial neuromuscular impairments. Few studies have investigated CKD-induced changes in maximal voluntary force (MVF), and even fewer have longitudinal follow-up. The aim of this study is to investigate whether CKD progression modifies the relationship between skeletal muscle mass and force and the prevalence of sarcopenia and sarcopenic obesity. Methods The data used were prospectively collected during routine check-ups in a network of nutritional centres in Mexico and retrospectively analysed. From a dataset of 5430 patients, we selected 1098 patients with available anthropometric, kidney function, handgrip and bioimpedance data. The relationship between appendicular skeletal muscle mass (ASM) and MVF was investigated using mixed models and adjusted for age, sex, BMI, physical activity level and CKD aetiology. Sarcopenia prevalence were tested across period of follow-up using the Cochran-Mantel-Haenzen for repeated measures and across CKD stages using the Chi-2 test. Results After normalization with ASM, MVF was higher in CKD G1-G3 compared to G4 and G5 (p ≤ 0.001, Cohen's d = 0.270–0.576). Slopes between MVF and ASM were lower in CKD G3, G4 and G5 than in CKD G1-G2 (-2.268 [-3.927,-0.609], p = 0.008; -2.694 [-4.593,-0.794], p = 0.006; -3.675 [-5.326,-1.725], p &amp;lt; 0.001, respectively). The prevalence of sarcopenia and sarcopenic obesity did not differ across CKD stages, but recovery was most commonly observed in CKD G1-G2. Slope analysis showed an independent interaction between the slopes of kidney function and ASM on MVF evolution over time. Conclusions CKD negatively, progressively and independently affects the neuromuscular system, and force production is reduced for any given muscle mass as CKD progresses. While no association was found between CKD stage and prevalence of sarcopenia, recovery was more frequent in the early CKD stages. These results suggest the importance of early rehabilitation programs to improve musculoskeletal health, quality of life and survival in CKD patients.

Augmentation of the Ulnar Motor Nerve Repair with Anterior Interosseous Nerve in High Ulnar Nerve Palsy: Our Clinical Experience

AbstractFollowing proximal ulnar nerve repair, there will be a delay in innervating the distally placed intrinsic muscles of the hand, which can lead to irreversible damage to the intrinsic motor end plates. Supercharging with end-to-side anterior interosseous nerve (AIN) transfer can augment the results of nerve repair by babysitting the motor end plates and thus preventing its denervation. Recently, there have been discussions regarding whether AIN, which contains only 500 axons, can augment the ulnar motor branch, which contains approximately 1,500 axons. In one of our cases, electromyogram following surgery showed activity in the first dorsal interossei and abductor digiti minimi without any signs of reinnervation in the flexor carpi ulnaris. This may support the contribution of AIN in supplying the intrinsic muscles. Considering the low morbidity of the procedure and potential improvements in muscle strength, all patients undergoing ulnar nerve repair in high ulnar nerve palsies can be counseled to undergo an end-to-side AIN transfer.

Physiological mechanisms of neuromuscular impairment in diabetes-related complications: Can physical exercise help prevent it?

Diabetes mellitus is a chronic disorder that progressively induces complications, compromising daily independence. Among these, diabetic neuropathy is particularly prevalent and contributes to substantial neuromuscular impairments in both types 1 and 2 diabetes. This condition leads to structural damage affecting both the central and peripheral nervous systems, resulting in a significant decline in sensorimotor functions. Alongside neuropathy, diabetic myopathy also contributes to muscle impairment and reduced motor performance, intensifying the neuromuscular decline. Diabetic neuropathy typically implicates neurogenic muscle atrophy, motoneuron loss and clustering of muscle fibres as a result of aberrant denervation-reinervation processes. These complications are associated with compromised neuromuscular junctions, where alterations occur in pre-synaptic vesicles, mitochondrial content and post-synaptic signalling. Neural damage is intensified by chronic hyperglycaemia and oxidative stress, exacerbating vascular dysfunction and reducing oxygen delivery. These complications imply a severe decline in neuromuscular performance, evidenced by reductions in maximal force and power output, rate of force development and muscle endurance. Furthermore, diabetes-related complications are compounded by age-related degenerative changes in long-term patients. Aerobic and resistance training offer promising approaches for managing blood glucose levels and neuromuscular function. Aerobic exercise promotes mitochondrial biogenesis and angiogenesis, supporting metabolic and cardiovascular health. Resistance training primarily enhances neural plasticity, muscle strength and hypertrophy, which are crucial factors for mitigating sarcopenia and preserving functional independence. This topical review examines current evidence on the physiological mechanisms underlying diabetic neuropathy and the potential impact of physical activity in counteracting this decline.

End Plate Chondrocyte-Derived Exosomal miR-133a-3p Alleviates Intervertebral Disc Degeneration by Targeting the NF-κB Signaling Pathway through the miR-133a-3p/MAML1 Axis.

Chondrocyte-derived exosomes have shown efficacy in differentiating osteoarthritis-affected cartilage. Intervertebral disc degeneration (IVDD) and osteoarthritis often affect facet joints of the spine and show common epidemiological and pathophysiological characteristics. However, the potential of chondrocyte-derived exosomes for treating IVDD remains unclear. The present study aimed to confirm the effect of end plate chondrocyte-derived exosomes (EPC-Exo) on IVDD and elucidate the underlying mechanism. EPC-Exos were isolated and identified by ultracentrifugation, Western blotting, electron microscopy, and nanoparticle tracking analysis. In the in vitro, EPC-Exo uptake by nucleus pulposus (NP) cells reduced cell death by blocking the nuclear factor-κB (NF-κB) signaling pathway. In the in vivo study, EPC-Exos injected into rat intervertebral discs mitigated lipopolysaccharide-induced IVDD, as revealed by a decreased loss of disc height and improved magnetic resonance imaging findings and histological scores. Bioinformatics and sequencing analyses indicated that EPC-Exos alleviated IVDD through the miR-133a-3p/MAML1 axis. The present study suggests that EPC-Exos reduced IVDD incidence via the miR-133a-3p/MAML1 axis-mediated suppression of NF-κB signaling, which prevented the pyroptosis of NP cells.

Nonlinear Gait Variability Increases with Age in Children from 2–10 Years Old

Background: Linear methods of analysis of variability are concerned with the magnitude of variability and often consider deviations from a central mean as errors. The utilization of nonlinear tools to examine variability allows for the exploration and measurement of the patterns of variability displayed by the system. This methodology explores the deterministic properties of biological signals, in this case, gait, or how previous iterations within the gait cycle influence subsequent and future iterations. The nonlinear analysis of gait variability of the joint angle time series has not been investigated in developing children. Methods: We collected 3 min of treadmill walking data for 28 children between the ages of 2 and 10 years old and analyzed their joint angle time series using nonlinear methods of analysis (sample entropy, largest Lyapunov exponent, and recurrence quantification analysis). Results: Our results indicate that the nonlinear variability of children’s gait increases as children age. Interestingly, this contrasts with the findings from our previous work that showed a decrease in linear variability as children age. The combination of a decrease in linear variability, or a refined and improved stability of gait, as well as an increase in nonlinear variability, or an increase in the sophistication and quality of movement patterns, suggest an overall maturation of the neuromuscular system. Conclusions: Our study indicate that there is a refining of gait with age and motor maturation. This refining speaks to the overall multifaceted organization of systems that defines the maturation of gait.

Sustainable Transportation Solutions in Remote Areas: Static Analysis of Vertical Axis Wind Turbines for Enhanced Efficiency of Wind-Powered Cars

It is imperative that a sustainable transportation system, powered by renewable energy resources, be implemented in order to mitigate the impacts of climate change and enhance living standards. A Wind-Powered Car (WPC) is a vehicle that employs a connection between the vehicle and wind turbine blades, thereby leveraging the advantages of wind kinetic energy. The energy is then conveyed directly to the car's wheels via a system of mechanical connections and gears, enabling the vehicle to move without the use of fossil fuels. The absence of an internal combustion engine results in the generation of negligible emissions. The primary objective of this study is to examine the static aerodynamic drag of nine WPC designs with diverse blade configurations of Vertical Axis Wind Turbines (VAWT). To achieve this objective, Autodesk Computational Fluid Dynamics (CFD) was employed to model the aerodynamic drag of WPC designs at varying wind speeds of 4 m/s, 6 m/s, and 8 m/s. The comparative analysis revealed that model 8, featuring a 3-blade Savonius wind turbine without a circular end plate, demonstrated superior efficiency among all car models. This is evident in its ability to generate the highest mechanical power compared to other blade designs. These findings contribute to the understanding of aerodynamic performance in VAWT cars, offering valuable insights for further design optimization. Furthermore, the results highlight model 8 as a promising solution for sustainable transportation, aligned with SDG 7 and SDG 11, through the development of clean and efficient wind-powered vehicles.

Reactive oxygen species in skeletal muscle injury, fatigue, regeneration and ageing: In memory of John Faulkner

One of the most critical factors impacting healthspan in the elderly is the loss of muscle mass and function, clinically referred to as sarcopenia. Muscle atrophy and weakness lead to loss of mobility, increased risk of injury, metabolic changes and loss of independence. Thus, defining the underlying mechanisms of sarcopenia is imperative to enable the development of effective interventions to preserve muscle function and quality in the elderly and improve healthspan. Over the past few decades, understanding the roles of mitochondrial dysfunction and oxidative stress has been a major focus of studies seeking to reveal critical molecular pathways impacted during aging. In this review, we will highlight how oxidative stress might contribute to sarcopenia by discussing the impact of oxidative stress on the loss of innervation and alteration in the neuromuscular junction (NMJ), on muscle mitochondrial function and atrophy pathways, and finally on muscle contractile function.

BoNT/Action beyond neurons.

Botulinum neurotoxin type A (BoNT/A) has expanded its therapeutic uses beyond neuromuscular disorders to include treatments for various pain syndromes and neurological conditions. Originally recognized for blocking acetylcholine release at neuromuscular junctions, BoNT/A's effects extend to both peripheral and central nervous systems. Its ability to undergo retrograde transport allows BoNT/A to modulate synaptic transmission and reduce pain centrally, influencing neurotransmitter systems beyond muscle control. BoNT/A also interacts with glial cells, such as Schwann cells, satellite glial cells, astrocytes, microglia, and oligodendrocytes. Schwann cells, key to peripheral nerve regeneration, are directly influenced by BoNT/A, which promotes their proliferation and enhances remyelination. Satellite glial cells, involved in sensory neuron regulation, show reduced glutamate release in response to BoNT/A, aiding in pain relief. In the CNS, BoNT/A modulates astrocyte activity, reducing excitotoxicity and inflammation, which is relevant in conditions like epilepsy. Microglia, the CNS's immune cells, shift from a pro-inflammatory to a neuroprotective state when treated with BoNT/A, enhancing tissue repair. Additionally, BoNT/A promotes oligodendrocyte survival and remyelination, especially after spinal cord injury. Overall, BoNT/A's ability to target both neurons and glial cells presents a multifaceted therapeutic strategy for neurological disorders, pain management, and CNS repair. Further research is necessary to fully elucidate its mechanisms and optimize its clinical application.

The Impact of Chronic Magnesium Deficiency on Excitable Tissues-Translational Aspects.

Neuromuscular excitability is a vital body function, and Mg2+ is an essential regulatory cation for the function of excitable membranes. Loss of Mg2+ homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg2+ deficiency is an increasingly prevalent condition in the general population. It is associated with an elevated risk of cardiovascular, respiratory and neurological conditions and an increased mortality. Magnesium favours bronchodilation (by antagonizing Ca2+ channels on airway smooth muscle and inhibiting the release of endogenous bronchoconstrictors). Magnesium exerts antihypertensive effects by reducing peripheral vascular resistance (increasing endothelial NO and PgI2 release and inhibiting Ca2+ influx into vascular smooth muscle). Magnesium deficiency disturbs heart impulse generation and propagation by prolonging cell depolarization (due to Na+/K+ pump and Kir channel dysfunction) and dysregulating cardiac gap junctions, causing arrhythmias, while prolonged diastolic Ca2+ release (through leaky RyRs) disturbs cardiac excitation-contraction coupling, compromising diastolic relaxation and systolic contraction. In the brain, Mg2+ regulates the function of ion channels and neurotransmitters (blocks voltage-gated Ca2+ channel-mediated transmitter release, antagonizes NMDARs, activates GABAARs, suppresses nAChR ion current and modulates gap junction channels) and blocks ACh release at neuromuscular junctions. Magnesium exerts multiple therapeutic neuroactive effects (antiepileptic, antimigraine, analgesic, neuroprotective, antidepressant, anxiolytic, etc.). This review focuses on the effects of Mg2+ on excitable tissues in health and disease. As a natural membrane stabilizer, Mg2+ opposes the development of many conditions of hyperexcitability. Its beneficial recompensation and supplementation help treat hyperexcitability and should therefore be considered wherever needed.

Bioelectricity is a universal multifaced signaling cue in living organisms.

The cellular electrical signals of living organisms were discovered more than a century ago and have been extensively investigated in the neuromuscular system. Neuronal depolarization and hyperpolarization are essential for our neuromuscular physiological and pathological functions. Bioelectricity is being recognized as an ancient, intrinsic, fundamental property of all living cells, and it is not limited to the neuromuscular system. Instead, emerging evidence supports a view of bioelectricity as an instructional signaling cue for fundamental cellular physiology, embryonic development, regeneration, and human diseases, including cancers. Here, we highlight the current understanding of bioelectricity and share our views on the challenges and perspectives.

Mitochondrial ROS modulate presynaptic plasticity in the drosophila neuromuscular junction.

The elevated emission of reactive oxygen species (ROS) from presynaptic mitochondria is well-documented in several inflammatory and neurodegenerative diseases. However, the potential role of mitochondrial ROS in presynaptic function and plasticity remains largely understudied beyond the context of disease. Here, we investigated this potential ROS role in presynaptic function and short-term plasticity by combining optogenetics, whole cell electrophysiological recordings, and live confocal imaging using a well-established protocol for induction and measurement of synaptic potentiation in Drosophila melanogaster neuromuscular junctions (NMJ). Optogenetic induction of ROS emission from presynaptic motorneuron mitochondria expressing mitokiller red (mK) resulted in synaptic potentiation, evidenced by an increase in the frequency of spontaneous mini excitatory junction potentials. Notably, this effect was not observed in flies co-expressing catalase, a cytosolic hydrogen peroxide (H2O2) scavenging enzyme. Moreover, the increase in electrical activity did not coincide with synaptic structural changes. The absence of Wnt1/Wg release from synaptic boutons suggested involvement of alternative or non-canonical signaling pathway(s). However, in existing boutons we observed an increase in the active zone (AZ) marker Brp/Erc1, which serves as docking site for the neurotransmitter vesicle release pool. We propose the involvement of putative redox switches in AZ components as the molecular target of mitochondrial H2O2. These findings establish a novel framework for understanding the signaling role of mROS in presynaptic structural and functional plasticity, providing insights into redox-based mechanisms of neuronal communication.