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Anastomose Cirúrgica , Endossonografia , Humanos , Endossonografia/métodos , Constrição Patológica/cirurgia , Constrição Patológica/etiologia , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Ultrassonografia de Intervenção , Masculino , Jejunostomia/métodos , Jejuno/cirurgia , Feminino , Colestase/cirurgia , Colestase/etiologia , Colestase/diagnóstico por imagem , Pessoa de Meia-Idade , IdosoRESUMO
Neuromuscular signal transmission is affected in various diseases including myasthenia gravis, congenital myasthenic syndromes, and sarcopenia. We used an ATF2-luciferase system to monitor the phosphorylation of MuSK in HEK293 cells introduced with MUSK and LRP4 cDNAs to find novel chemical compounds that enhanced agrin-mediated acetylcholine receptor (AChR) clustering. Four compounds with similar chemical structures carrying benzene rings and heterocyclic rings increased the luciferase activities 8- to 30-folds, and two of them showed continuously graded dose dependence. The effects were higher than that of disulfiram, a clinically available aldehyde dehydrogenase inhibitor, which we identified to be the most competent preapproved drug to enhance ATF2-luciferase activity in the same assay system. In C2C12 myotubes, all the compounds increased the area, intensity, length, and number of AChR clusters. Three of the four compounds increased the phosphorylation of MuSK, but not of Dok7, JNK. ERK, or p38. Monitoring cell toxicity using the neurite elongation of NSC34 neuronal cells as a surrogate marker showed that all the compounds had no effects on the neurite elongation up to 1 µM. Extensive docking simulation and binding structure prediction of the four compounds with all available human proteins using AutoDock Vina and DiffDock showed that the four compounds were unlikely to directly bind to MuSK or Dok7, and the exact target remained unknown. The identified compounds are expected to serve as a seed to develop a novel therapeutic agent to treat defective NMJ signal transmission.
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Receptores Nicotínicos , Humanos , Células HEK293 , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Animais , Camundongos , Fosforilação/efeitos dos fármacos , Simulação de Acoplamento Molecular , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/químicaRESUMO
BACKGROUND: Although biofeedback with contingent electrical stimulation (CES) has demonstrated the reduction effect on sleep bruxism (SB), the relationship between the actual applied CES intensity and efficacy remains uncertain. OBJECTIVE: This study aimed to investigate whether the reduction of bruxism events and jaw muscle symptoms could vary according to the intensity of CES and in probable sleep bruxers. METHODS: Twenty probable sleep bruxers were initially screened for bruxer confirmation based on a 2-week recording of SB events with a portable electromyography recorder (BUTLER®GrindCare®, GC4). A 3-week recording was conducted without CES using a GC4, followed by another 3-week recording with CES. At baseline and before and after the CES (+) session, clinical muscle symptoms were assessed using a 0-10 numerical rating scale (NRS). The relationships between the actual applied CES intensity and the number of SB events/hour, as well as the NRS of clinical muscle symptoms, were analysed. RESULTS: The actual applied CES intensity was positively correlated with the reduction rate of the number of SB events/hour (R = .643, p = .002), as well as with the reduction rate of NRS for pain, unpleasantness, fatigue, tension and stiffness (R > .500, p < .011). CONCLUSION: Higher CES elicited a more robust reduction in SB events and clinical muscle symptoms, in probable bruxers. Prior to selecting CES biofeedback as a management option for SB, it would be beneficial to assess the tolerance threshold of CES in each bruxer in order to predict the effectiveness of CES in probable sleep bruxers.
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Terapia por Estimulação Elétrica , Eletromiografia , Bruxismo do Sono , Humanos , Bruxismo do Sono/terapia , Bruxismo do Sono/fisiopatologia , Bruxismo do Sono/complicações , Masculino , Feminino , Adulto , Terapia por Estimulação Elétrica/métodos , Resultado do Tratamento , Adulto Jovem , Biorretroalimentação Psicológica/métodosRESUMO
PURPOSE: To report the surgical outcome of synovial osteochondromatosis, a rare tumor of the cervical spine, in a 6-year-old boy. METHODS: A 6-year-old boy presented with muscle weakness in the right deltoid (2) and biceps (4) during a manual muscle test. Magnetic resonance imaging showed a 3 × 2 × 1.5 cm mass within the spinal canal at the C4-6 level, compressing the cervical spinal cord from the right side. Computed tomography revealed hyperintense areas within the tumor and ballooning of the right C4-5 and C5-6 facet joints. RESULTS: After a biopsy confirmed the absence of malignancy, a gross total resection was performed. The pathological diagnosis of synovial osteochondromatosis was established. Postoperatively, muscle weakness improved fully in the manual muscle test, and there were no neurological findings after 3 months. However, the patient is under careful follow-up owing to the detection of a regrowth site within the right C4-5 and C5-6 intervertebral foramen 2 years postoperatively. CONCLUSIONS: Synovial osteochondromatosis of the cervical spine in children is rare, and this is the first report of its regrowth after surgery. Synovial osteochondromatosis should be included in the differential diagnosis of pediatric cervical spine tumors.
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Vértebras Cervicais , Condromatose Sinovial , Laminectomia , Humanos , Masculino , Criança , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Laminectomia/métodos , Condromatose Sinovial/cirurgia , Condromatose Sinovial/diagnóstico por imagem , Paralisia/etiologia , Paralisia/cirurgia , Resultado do Tratamento , Recuperação de Função Fisiológica , Compressão da Medula Espinal/cirurgia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including congenital myasthenic syndromes (CMS). Germline mutations in CHRNE encoding the acetylcholine receptor (AChR) ε subunit are the most common cause of CMS. An active form of vitamin D, calcitriol, binds to vitamin D receptor (VDR) and regulates gene expressions. We found that calcitriol enhanced MuSK phosphorylation, AChR clustering, and myotube twitching in co-cultured C2C12 myotubes and NSC34 motor neurons. RNA-seq analysis of co-cultured cells showed that calcitriol increased the expressions of Rspo2, Rapsn, and Dusp6. ChIP-seq of VDR revealed that VDR binds to a region approximately 15 âkbp upstream to Rspo2. Biallelic deletion of the VDR-binding site of Rspo2 by CRISPR/Cas9 in C2C12 myoblasts/myotubes nullified the calcitriol-mediated induction of Rspo2 expression and MuSK phosphorylation. We generated Chrne knockout (Chrne KO) mouse by CRISPR/Cas9. Intraperitoneal administration of calcitriol markedly increased the number of AChR clusters, as well as the area, the intensity, and the number of synaptophysin-positive synaptic vesicles, in Chrne KO mice. In addition, calcitriol ameliorated motor deficits and prolonged survival of Chrne KO mice. In the skeletal muscle, calcitriol increased the gene expressions of Rspo2, Rapsn, and Dusp6. We propose that calcitriol is a potential therapeutic agent for CMS and other diseases with defective neuromuscular signal transmission.
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Síndromes Miastênicas Congênitas , Animais , Camundongos , Síndromes Miastênicas Congênitas/tratamento farmacológico , Síndromes Miastênicas Congênitas/genética , Síndromes Miastênicas Congênitas/metabolismo , Calcitriol/metabolismo , Junção Neuromuscular/metabolismo , Receptores Colinérgicos/genética , Receptores Colinérgicos/metabolismo , Neurônios Motores/metabolismoRESUMO
We report the case of a 65-year-old woman whose colonoscopy revealed a soft submucosal tumor approximately 7 cm in diameter in the ascending colon with an overlying flat lesion. The tumor was diagnosed as a lipoma with an overlying adenoma. Endoscopic submucosal dissection (ESD) was performed. Pathological examination revealed that the epithelium was a low-grade tubulovillous adenoma, while the submucosal yellow tumor was a lipoma. ESD appears to be a safe and effective treatment for colorectal lipomas overlying lipomas with colorectal adenomas.
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BACKGROUND: The assessment of masticatory performance (MP) is conducted in hospitals, but is difficult to perform in nursing facilities that lack specialists in dysphagia. To select the appropriate food textures in nursing practice, a simple method of evaluating the MP should be developed. OBJECTIVE: The purpose of this study was to investigate motion parameters that influence MP by motion capture analysis of maxillofacial movement on chewing gummy jelly in healthy adults. METHODS: The subjects were 50 healthy adults. The state of chewing gummy jelly was photographed using a high-speed camera. Simultaneously, we evaluated the amount of glucose extracted (AGE) obtained with gummy jelly as a reference value for MP. The subjects were divided into two groups: normal and low masticatory groups (NG and LG, respectively) based on the AGE. The cycle of mastication was classified into three phases: closing phase (CP), transition phase (TP) and opening phase (OP) through motion capture analysis of the video photographed. Parameters of jaw movement and their associations with the AGE were examined. RESULTS: The transition phase rate (TR) and opening phase rate (OR) were correlated with the AGE. Furthermore, the TR in the NG was significantly higher than in the LG, whereas the OR was significantly lower than in the LG. The age, TR and opening velocity were significant independent variables. CONCLUSION: Motion capture technology facilitated the analysis of jaw movement. The results suggested that MP can be evaluated by analysing the TP and OP rates.
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Mastigação , Captura de Movimento , Adulto , Humanos , Alimentos , Movimento , Goma de MascarRESUMO
BACKGROUND: Excess visceral fat can accumulate owing to lack of exercise. The relationship between metabolic syndrome (MetS) and spinal range of motion (ROM) is not clear. The purpose of this study was to investigate the relationship between MetS and spinal alignment and ROM. METHODS: Orthopedic evaluation was prospectively performed in 544 participants. The participants were classified into two groups on the basis of the Japanese-specific MetS criteria proposed by the Japanese Committee of the Criteria for MetS (JCCMS). Lower back pain (LBP), knee joint pain with the visual analog scale (VAS), Kellgren-Lawrence (K-L) grade for knee osteoarthritis, body mass index (BMI), and spinal alignment and ROM were evaluated. RESULTS: Forty-four (8.1%) were diagnosed as having MetS. The prevalence rate of K-L grade 4 in the MetS group was significantly higher than that in the non-MetS group (p < 0.05). When sex, age, and BMI were evaluated as covariates, there were significant differences in the VAS score for knee pain (non-MetS group vs MetS group: 13.7 vs 23.3, p < 0.05), L1-S1 flexion spinal ROM (44.1° vs 38.1°, p < 0.001), flexion spinal inclination angle (SIA) ROM (107.6° vs 99.3°, p < 0.01), and SIA ROM (135.4° vs 124.0°, p < 0.05). CONCLUSIONS: Knee pain increased and flexion spinal ROM decreased significantly in the MetS group as compared with non-MetS group. Systemic factors associated with MetS may have a specific impact on spinal ROM while promoting knee osteoarthrosis and increased knee pain.
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Dor Lombar , Síndrome Metabólica , Osteoartrite do Joelho , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Coluna Vertebral , Articulação do Joelho , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/complicações , Dor Lombar/diagnóstico , Dor Lombar/epidemiologia , Dor Lombar/complicações , Amplitude de Movimento ArticularRESUMO
The diagnosis of pediatric spinal cord tumor is frequently delayed due to the presence of non-specific symptoms. We investigated the factors influencing the delay between the first symptom presentation and the diagnosis for pediatric spinal cord tumor. We retrospectively analyzed 31 patients of age <20 years (18 men, 13 women) who underwent surgery for spinal cord tumor at a single center during 1998-2018. We extracted the relevant data on patients' symptoms, affected spinal location (cervical: C1-7, thoracic: T1-T12, and lumbosacral: L1-S), and tumor anatomical location (extradural, intradural extramedullary, and intramedullary tumor) that could potentially affect the duration of symptom presentation prior to the diagnosis. The most common symptom presented in the patients was pain (n = 22, 71.0 %). Motor symptoms such as paralysis was associated with early diagnosis (P = 0.039). The duration of symptoms prior to diagnosis was found to be significantly longer in patients with spinal tumor in the lumbar-sacral region than in those with the involvement of the cervical and thoracic regions (2.1 ± 1.7 months vs 13.6 ± 12.1 months; P = 0.006 and 2.9 ± 2.2 months vs 13.6 ± 12.1 months; P = 0.012, respectively). Our study results demonstrated that pain was the most common symptom in the examined patients, although it did not affect the delay in diagnosis, whereas the presentation of motor symptoms was helpful in the diagnosis of pediatric spinal cord tumor and the diagnosis could be delayed in lumbar-sacral spinal tumors.
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Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Adulto , Criança , Feminino , Humanos , Masculino , Dor , Estudos Retrospectivos , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/cirurgia , Adulto JovemRESUMO
BACKGROUND: Maintaining quality of life of elderly denture wearers is one of the most crucial tasks for dentists in the super-aged society. Although external mechanical load on removable dentures has been investigated to minimise a risk of soreness caused by dentures, sensory perception of the alveolar mucosa remains obscure. OBJECTIVES: This study aimed to investigate effect of ageing and tooth loss in sensory function on the alveolar mucosa for deep understanding of the characteristics of pain sensitivity in edentulous individuals. METHODS: Eighteen edentulous participants (ED), as well as 18 age-matched dentate participants (EC) and 18 young dentate participants (YC), participated in this study. Tactile detection threshold (TDT) and pain threshold (PT) were measured with von Frey filaments (0.125-512 mN). Mechanical pain sensitivity (MPS) after a 2-sec application of 1 kg palpation was assessed with a 0-50-100 Numerical Rating Scale (NRS) (0: no pain, 50: slight pain and 100: the worst pain imaginable). Furthermore, entropy scores of TDT, PT and NRS on MPS were calculated. RESULTS: In both maxilla and mandible, EC showed significantly higher TDT and PT, compared with YC, whereas ED showed significantly lower TDT and PT, compared with EC. NRS on MPS in ED was significantly higher than that in EC. The entropy scores of all the outcome parameters showed no significant difference between groups. CONCLUSION: Both ageing and tooth loss can alter tactile and pain perception in the oral mucosa. This suggests that it might be beneficial to assess sensory function of the alveolar mucosa in edentulous patients clinically in prior to denture fabrication.
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Perda de Dente , Idoso , Envelhecimento , Prótese Total , Humanos , Mucosa Bucal , Limiar da Dor , Qualidade de VidaRESUMO
An annual physical checkup is provided as part of the long-term Yakumo study. The checkup is voluntary and there is variation in the frequency of participation. The aim of this study was to examine relationship of physical fitness with frequency of participation in this checkup. The subjects had all attended at least one annual physical checkup from 2006 to 2018. Data from 1,804 initial checkups were used for analysis. At the checkups, age, gender, height, weight, body mass index (BMI), and bone mineral density (BMD) were recorded, and physical activity was measured. The average number of physical checkups per participant for 13 years was 2.4 (1-13). Daily exercise habits were found to be significantly associated with higher participation in physical checkups. Furthermore, between groups with low (1-5 times; <90th percentile of participants) and high (≥6 times) participation, weight and BMI were significantly higher, and BMD, grip strength, 10-m gait time, back muscle strength, and two-step test were all significantly lower in the group with lower frequency of participation in the checkup. In conclusions, our results show that frequency of participation in a voluntary annual physical checkup is significantly associated with physical fitness in middle-aged and elderly people.
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Nível de Saúde , Exame Físico/estatística & dados numéricos , Aptidão Física , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 48-year-old female patient presented with discomfort in the front of the chest. Whole spinal X-ray revealed a thoracic curve of 52°, and thoracic computed tomography (CT) myelography and magnetic resonance imaging (MRI) showed that ossification of the posterior longitudinal ligament (OPLL) on the concave side of the apex vertebra (T9) had highly compressed the spinal cord. Cervical MRI also showed that the C4-C5 intervertebral disc herniation mildly compressed the spinal nerve. In concomitant surgery, the patient underwent cervical laminoplasty, in which OPLL was removed by decompressive laminectomy and posterior correction surgery.In patients with adult spinal deformity (ASD), asymmetric mechanical stress at the apex vertebra can cause various abnormal conditions. Long-term local mechanical stress on the concave side of the apex vertebra might have affected OPLL formation in the present case. This is the first report of a surgical case for an ossification located on the concave side of the apex vertebra in a patient with ASD. Mechanical stress at the concave side of the apex vertebra was suspected to be a cause of formation of OPLL.
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Laminoplastia , Ossificação do Ligamento Longitudinal Posterior , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Feminino , Humanos , Ligamentos Longitudinais , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Osteogênese , Coluna VertebralRESUMO
The ratio of human nonmercaptalbumin (HNA) and reduced albumin (HMA) may be a new marker for oxidative stress. Locomotive syndrome (LS) is reduced mobility due to impairment of locomotive organs. We investigated whether the HNA/HMA ratio could be a new biomarker of LS. This study included 306 subjects (mean age 64.24 ± 10.4 years) who underwent LS tests, grip strength, walking speed, and tests for HNA and HMA. Oxidative stress was measured by the ratio of HMA (f(HMA) = (HMA/(HMA + HNA) × 100)), and the subjects were divided into normal (N group; f[HMA] ≥ 70%) and low (L group; f[HMA] < 70%) groups. There were 124 non-elderly (<65 years) and 182 elderly subjects (≥65 years). There were no significant differences in LS, grip strength, and walking speed between the L and N groups in the non-elderly subjects. However, significant differences were found in the elderly subjects. In logistic regression analysis, there was an association between f(HMA) and the LS severity at older ages. LS in the elderly is associated with a decline in HMA and, thus, an increase in oxidative stress. Thus, f(HMA) is a new biomarker of LS.
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PURPOSE: Neck and shoulder pain (NSP) is very common in the general population. However, scarce information exists on the relationship between NSP and health-related quality of life (HRQOL) outcomes in this population. The present study described NSP prevalence and its impact on the HRQOL of middle-aged and older persons undergoing a routine medical checkup. METHODS: This study recruited 318 subjects (125 males and 193 females; average age, 63.4 years) in good health, collected underwent anthropometric measurements, physical function examinations, and blood testing. This study defined NSP as the presence of muscle tension, stiffness, pressure, or dull pain in areas between the neck and the arch of the scapular. Study subjects were divided into two groups (NSP (+) and NSP (-) groups). The subjects completed questions on the Medical Outcomes Study 36-item short-form health survey (SF-36) and the EuroQol 5-dimension, 5-level version (EQ-5D-5L) tool. RESULTS: Of the patients, 150 and 168 were NSP (+) and NSP (-), respectively. The NSP complaint rate was 47.2%. The NSP (+) group had younger and more female participants than the NSP (-) group. In the multivariate regression analysis, the NSP (+) group had lower physical QOL based on the SF-36 physical component summary (odds ratio (OR), 2.45) and lower mental QOL based on the SF-36 mental component summary (OR, 2.05). Overall, the NSP (+) group had a higher risk of having low QOL scores (EQ-5D-5L index; OR, 1.76). CONCLUSIONS: The NSP (+) rate in healthy middle-aged and older persons was 47.2%. Furthermore, NSP (+) status was directly related poor HRQOL. NSP is a predictor of suboptimal physical and mental QOL. Therefore, NSP prevention or intervention for NSP may improve middle-aged and older adults' QOL.
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Cervicalgia/fisiopatologia , Pescoço/fisiopatologia , Dor de Ombro/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/fisiopatologia , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
PURPOSE: To quantify calcification in spinal meningiomas using Hounsfield unit (HU) values on CT, and to analyze the characteristics of cases with and without calcification and with different histologic subtypes. METHODS: The subjects were 53 patients who underwent surgical resection of spinal meningioma between January 1999 and December 2019. Clinical and surgical data were collected, and all patients were examined neurologically preoperatively and at final follow-up using the modified McCormick scale and the American Spinal Injury Association scale. Calcification was quantified on CT of the spine prior to surgery. A HU value >60 was considered to indicate calcification. RESULTS: The 53 patients (11 males, 42 females) were aged 62.4 ± 14.3 (range 19 to 91) years at surgery, and had a symptom duration of 10.8 ± 9.0 (1-36) months. The histological type was meningothelial in 35 cases, psammomatous in 13, and others in 5. The mean tumor volume was 1166 ± 350 (593-2176) mm3, and the mean HU value was 212.2 ± 192.8 (43-648). Forty cases (75%) had calcification (HU value > 60). HU values were significantly related to duration of symptoms (R = 0.590, p < 0.05) and significantly higher in psammomatous cases (p < 0.05). Cases with calcification had longer operative times and greater blood loss, and a significantly lower rate of neurological improvement. CONCLUSION: CT was effective for detecting calcification based on HU values. Detection of a HU value > 60 in spinal meningioma may be useful to narrow the differential diagnosis, evaluate the difficulty of resection, and improve intraoperative management, all of which may improve outcomes.
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Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Carga Tumoral , Adulto JovemRESUMO
Decreased acetylcholine receptor (AChR) clustering compromises signal transmission at the neuromuscular junction (NMJ) in myasthenia gravis, congenital myasthenic syndromes, and motor neuron diseases. Although the enhancement of AChR clustering at the NMJ is a promising therapeutic strategy for these maladies, no drug is currently available for this enhancement. We previously reported that zonisamide (ZNS), an anti-epileptic and anti-Parkinson's disease drug, enhances neurite elongation of the primary spinal motor neurons (SMNs). As nerve sprouting occurs to compensate for the loss of AChR clusters in human diseases, we examined the effects of ZNS on AChR clustering at the NMJ. To this end, we established a simple and quick co-culture system to reproducibly make in vitro NMJs using C2C12 myotubes and NSC34 motor neurons. ZNS at 1-20 µM enhanced the formation of AChR clusters dose-dependently in co-cultured C2C12 myotubes but not in agrin-treated single cultured C2C12 myotubes. We observed that molecules that conferred responsiveness to ZNS were not secreted into the co-culture medium. We found that 10 µM ZNS upregulated the expression of neuregulin-1 (Nrg1) in co-cultured cells but not in single cultured C2C12 myotubes or single cultured NSC34 motor neurons. In accordance with this observation, inhibition of the Nrg1/ErbB signaling pathways nullified the effect of 10 µM ZNS on the enhancement of AChR clustering in in vitro NMJs. Although agrin was not induced by 10 µM ZNS in co-cultured cells, anti-agrin antibody attenuated ZNS-mediated enhancement of AChR clustering. We conclude that ZNS enhances agrin-dependent AChR-clustering by upregulating the Nrg1/ErbB signaling pathways in the presence of NMJs.