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Browsing by Subject "Motor Neurons"
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Item Accurate and representative decoding of the neural drive to muscles in humans with multi-channel intramuscular thin-film electrodes(Wiley, 2015-09-01) Muceli, Silvia; Poppendieck, Wigand; Negro, Francesco; Yoshida, Ken; Hoffmann, Klaus P.; Butler, Jane E.; Gandevia, Simon C.; Farina, Dario; Department of Biomedical Engineering, School of Engineering and TechnologyIntramuscular electrodes developed over the past 80 years can record the concurrent activity of only a few motor units active during a muscle contraction. We designed, produced and tested a novel multi-channel intramuscular wire electrode that allows in vivo concurrent recordings of a substantially greater number of motor units than with conventional methods. The electrode has been extensively tested in deep and superficial human muscles. The performed tests indicate the applicability of the proposed technology in a variety of conditions. The electrode represents an important novel technology that opens new avenues in the study of the neural control of muscles in humans. We describe the design, fabrication and testing of a novel multi-channel thin-film electrode for detection of the output of motoneurones in vivo and in humans, through muscle signals. The structure includes a linear array of 16 detection sites that can sample intramuscular electromyographic activity from the entire muscle cross-section. The structure was tested in two superficial muscles (the abductor digiti minimi (ADM) and the tibialis anterior (TA)) and a deep muscle (the genioglossus (GG)) during contractions at various forces. Moreover, surface electromyogram (EMG) signals were concurrently detected from the TA muscle with a grid of 64 electrodes. Surface and intramuscular signals were decomposed into the constituent motor unit (MU) action potential trains. With the intramuscular electrode, up to 31 MUs were identified from the ADM muscle during an isometric contraction at 15% of the maximal force (MVC) and 50 MUs were identified for a 30% MVC contraction of TA. The new electrode detects different sources from a surface EMG system, as only one MU spike train was found to be common in the decomposition of the intramuscular and surface signals acquired from the TA. The system also allowed access to the GG muscle, which cannot be analysed with surface EMG, with successful identification of MU activity. With respect to classic detection systems, the presented thin-film structure enables recording from large populations of active MUs of deep and superficial muscles and thus can provide a faithful representation of the neural drive sent to a muscle.Item Altered mRNA Splicing in SMN-Depleted Motor Neuron-Like Cells(Public Library of Science (PLoS), 2016) Custer, Sara K.; Gilson, Timra D.; Li, Hongxia; Todd, A. Gary; Astroski, Jacob W.; Lin, Hai; Liu, Yunlong; Androphy, Elliot J.; Department of Dermatology, School of MedicineSpinal muscular atrophy (SMA) is an intractable neurodegenerative disease afflicting 1 in 6-10,000 live births. One of the key functions of the SMN protein is regulation of spliceosome assembly. Reduced levels of the SMN protein that are observed in SMA have been shown to result in aberrant mRNA splicing. SMN-dependent mis-spliced transcripts in motor neurons may cause stresses that are particularly harmful and may serve as potential targets for the treatment of motor neuron disease or as biomarkers in the SMA patient population. We performed deep RNA sequencing using motor neuron-like NSC-34 cells to screen for SMN-dependent mRNA processing changes that occur following acute depletion of SMN. We identified SMN-dependent splicing changes, including an intron retention event that results in the production of a truncated Rit1 transcript. This intron-retained transcript is stable and is mis-spliced in spinal cord from symptomatic SMA mice. Constitutively active Rit1 ameliorated the neurite outgrowth defect in SMN depleted NSC-34 cells, while expression of the truncated protein product of the mis-spliced Rit1 transcript inhibited neurite extension. These results reveal new insights into the biological consequence of SMN-dependent splicing in motor neuron-like cells.Item Morphologic Changes in the Mandibular Condyle of Growing Sprague-Dawley Rats After Electrolytic Lesioning of the Trigeminal Motor Nucleus(1994) Hurst, Charles A.; Byrd, Kenneth E.; Roberts, W. Eugene; Garetto, Lawrence P.; Hohlt, William; Burr, DavidLesioning motoneurons in the brainstem alters biomechanical forces and affects craniofacial growth by producing skeletal asymmetries. The purpose of this study was to examine changes that occur in the mandibular condyle in rats that have had their trigeminal motor nucleus (TMN) lesioned. The following null hypothesis was tested: unilateral electrolytic lesioning of the TMN has no effect on condylar morphology in growing rats. To accomplish this, experimental rats received a small electrolytic lesion in their left side TMN. The controls received a sham lesion that caused TMN stimulation with no electrolytic lesion produced. Seven rats from each group were sacrificed at 28, 56, and 84 days postoperatively. The rats were decapitated and their skulls were dried. Mandibular condyles were harvested from the dry rat skulls. The specimens were embedded and sectioned. The sections were stained with H&E. The following parameters were measured: condyle perimeter, condylar widths at 125 μm increments measured with a grid aligned with the condylar neck, width of the condylar neck, and bone surface area proximal to the condylar neck measurement. Experimental groups were compared with control groups by means of factorial analysis of variance, ANOVA, with the factors being the experimental operation and the time of sacrifice. Findings show significant or near borderline significant F tests for right-left differences and side-by-group interactions for width at 625 μm, 750 μm, 875 μm, and 1000 μm from the top of the condyle; but not at the other widths measured. Right-left difference and side-by-time interaction for shape factor measurement were also shown to be significant. The null hypothesis stating unilateral electrolytic lesioning of the TMN has no effect on condylar morphology in growing rats was therefore rejected. The failure to reach significance in some parameters may have been due to the small number of specimens. Due to the fragile nature of the dried specimens, group numbers ranged from seven to four condyle pairs per group. In conclusion, lesions to the TMN of growing rats affect the morphology of the mandibular condyle in the medial-lateral plane. Alterations in morphology during growth after lesioning the TMN were likely caused by changes in the neuromuscular activity of masticatory muscles and their biomechanical effects on bone. Data in this study suggest that it is valuable to view mandibular condyles from a frontal view (i.e., frontal tomography) when altered condylar morphology in human patients is suspected.Item PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury(Elsevier, 2014-06-24) Walker, Chandler L.; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineCervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; p < 0.01) and Luxol Fast Blue (LFB)+ myelin area rostral (Veh: 0.56 ± 0.01 vs. bpV: 0.64 ± 0.02; p < 0.05) and at the epicenter (Veh: 0.4175 ± 0.03 vs. bpV: 0.5400 ± 0.03; p < 0.05). VLF oligodendrocytes were also significantly greater with bpV therapy (109 ± 5.3 vs. Veh: 77 ± 2.7/mm2; p < 0.01). In addition, bpV increased mean motor neuron soma area versus vehicle-treatment (1.0 ± 0.02 vs. Veh: 0.77 ± 0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI.Item Th17 Cell Response in SOD1G93A Mice following Motor Nerve Injury(Hindawi, 2016) Ni, Allen; Yang, Tao; Mesnard-Hoaglin, Nicole A.; Gutierrez, Rafael; Stubbs Jr., Evan B.; McGuire, Susan O.; Sanders, Virginia M.; Jones, Kathryn J.; Foecking, Eileen M.; Xin, Junping; Department of Anatomy & Cell Biology, IU School of MedicineAn increased risk of ALS has been reported for veterans, varsity athletes, and professional football players. The mechanism underlying the increased risk in these populations has not been identified; however, it has been proposed that motor nerve injury may trigger immune responses which, in turn, can accelerate the progression of ALS. Accumulating evidence indicates that abnormal immune reactions and inflammation are involved in the pathogenesis of ALS, but the specific immune cells involved have not been clearly defined. To understand how nerve injury and immune responses may contribute to ALS development, we investigated responses of CD4(+) T cell after facial motor nerve axotomy (FNA) at a presymptomatic stage in a transgenic mouse model of ALS (B6SJL SOD1(G93A)). SOD1(G93A) mice, compared with WT mice, displayed an increase in the basal activation state of CD4(+) T cells and higher frequency of Th17 cells, which were further enhanced by FNA. In conclusion, SOD1(G93A) mice exhibit abnormal CD4(+) T cell activation with increased levels of Th17 cells prior to the onset of neurological symptoms. Motor nerve injury exacerbates Th17 cell responses and may contribute to the development of ALS, especially in those who carry genetic susceptibility to this disease.