RESUMEN
INTRODUCTION/AIMS: Mental rotation (MR), a tool of implicit motor imagery, is the ability to rotate mental representations of two- or three-dimensional objects. Although many reports have described changes in brain activity during MR tasks, it is not clear whether the excitability of anterior horn cells in the spinal cord can be changed. In this study, we examined whether MR tasks of hand images affect the excitability of anterior horn cells using F-wave analysis. METHODS: Right-handed, healthy participants were recruited for this study. F-waves of the right abductor pollicis brevis were recorded after stimulation of the right median nerve at rest, during a non-MR task, and during an MR task. The F-wave persistence and the F/M amplitude ratio were calculated and analyzed. RESULTS: Twenty participants (11 men and 9 women; mean age, 29.2 ± 4.4 years) were initially recruited, and data from the 18 that met the inclusion criteria were analyzed. The F-wave persistence was significantly higher in the MR task than in the resting condition (p = .001) or the non-MR task (p = .012). The F/M amplitude ratio was significantly higher in the MR task than in the resting condition (p = .019). DISCUSSION: The MR task increases the excitability of anterior horn cells corresponding to the same body part. MR tasks may have the potential for improving motor function in patients with reduced excitability of the anterior horn cells, although this methodology must be further verified in a clinical setting.
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Células del Asta Anterior , Cuerpo Humano , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Células del Asta Anterior/fisiología , Músculo Esquelético/fisiología , Médula Espinal , Nervio Mediano/fisiología , Potenciales Evocados Motores/fisiología , ElectromiografíaRESUMEN
BACKGROUND: F-waves, which are an indicator of the excitability of spinal cord anterior horn cells, are characterized by diverse waveforms. However, no analytical method has yet been development that fully reflects the diversity of such waveforms. The present study examined whether or not the change in the amplitude by the additive averaging process reflects the dispersion of the peak. NEW METHOD: The average amplitude of each waveform and the decrease in the amplitude after the additive averaging process were determined. The correlation between the decrease in the amplitude and the density of the peak was then examined. The histogram was also used to classify the type of waveform dispersion based on the characteristics of the peak latency. RESULTS: No correlation was found between the change in the amplitude and the peak density. However, the F-waves obtained from the ulnar nerve of healthy subjects were able to be classified into five types. COMPARISON WITH EXISTING METHOD: The parameters of an F-wave analysis are the rise latency, the amplitude and the persistence, and many reports have examined F-waves based on the changes in these values. The present study explored new parameters focusing on the waveform of F-waves reflecting the motor unit. CONCLUSION: The results of this study may help to establish a standard of comparison when using the F wave to evaluate spasticity due to upper motor neuron disorders.
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Enfermedad de la Neurona Motora , Nervio Cubital , Células del Asta Anterior/fisiología , Electromiografía , Voluntarios Sanos , Humanos , Proyectos de Investigación , Nervio Cubital/fisiologíaRESUMEN
Astrocytes are thought to play a crucial role in providing structure to the spinal cord and maintaining efficient synaptic function and metabolism because their fine processes envelop the synapses of neurons and form many neuronal networks within the central nervous system (CNS). To investigate whether putative astrocytes and putative neurons distributed on the ventral horn play a role in the modulation of lumbar locomotor central pattern generator (CPG) networks, we used extracellular recording and optical imaging techniques and recorded the neural output from the left L5 ventral root and the calcium activity of putative astrocytes and neurons in the L5 ventral horn at the same time when activating an isolated L1-L5 spinal cord preparation from rats aged 0-2 days. Optical measurements detected cells that showed a fluorescence intensity change under all experimental conditions, namely, (1) 5-HT + NMDA, (2) TTX, and (3) TTX + Low K+. These cells were semiautomatically identified using an in-house MATLAB-based program, as putative astrocytes and neurons according to the cell classification, i.e., increased or decreased fluorescence intensity change (ΔF/F0), and subjective judgment based on their soma size. Coherence and its phase were calculated according to the calcium activity of the putative astrocytes and putative neurons, and neural output was calculated during fictive locomotion with in-house MATLAB-based programs. We found that the number of putative astrocytes activated by applying low K+ tends not to differ from that activated by applying the protease-activated receptor 1 (PAR1) selective agonist TFLLR-NH2 (TFLLR). Moreover, the calcium activity of several putative astrocytes and neurons synchronized with locomotor-like activity at a frequency range below 0.5 Hz and the time lag between peaks of cellular calcium activity and locomotor-like activity ranged from -1000 to + 1000 ms. These findings presumably indicates that these putative astrocytes and neurons in the left L5 ventral horn require -1000 to + 1000 ms to communicate with lumbar CPG networks and maintain efficient synaptic function and metabolism in activated lumbar CPG networks. This finding suggests the possibility that putative astrocytic and neuronal cells in the L5 ventral horn contribute to generating the rhythms and patterns of locomotor-like activity by activated CPG networks in the first to fifth lumbar spinal cord.
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Células del Asta Anterior/metabolismo , Astrocitos/metabolismo , Señalización del Calcio , Generadores de Patrones Centrales/metabolismo , Locomoción , Animales , Células del Asta Anterior/efectos de los fármacos , Células del Asta Anterior/fisiología , Astrocitos/efectos de los fármacos , Astrocitos/fisiología , Generadores de Patrones Centrales/efectos de los fármacos , Generadores de Patrones Centrales/fisiología , N-Metilaspartato/metabolismo , Oligopéptidos/farmacología , Potasio/metabolismo , Ratas , Ratas Wistar , Serotonina/metabolismo , Tetrodotoxina/farmacologíaRESUMEN
Neuroinflammation is an escalation factor shared by a vast range of central nervous system (CNS) pathologies, from neurodegenerative diseases to neuropsychiatric disorders. CNS immune status emerges by the integration of the responses of resident and not resident cells, leading to alterations in neural circuits functions. To explore spinal cord astrocyte reactivity to inflammatory threats we focused our study on the effects of local inflammation in a controlled micro-environment, the organotypic spinal slices, developed from the spinal cord of mouse embryos. These organ cultures represent a complex in vitro model where sensory-motor cytoarchitecture, synaptic properties and spinal cord resident cells, are retained in a 3D fashion and we recently exploit these cultures to model two diverse immune conditions in the CNS, involving different inflammatory networks and products. Here, we specifically focus on the tuning of calcium signaling in astrocytes by these diverse types of inflammation and we investigate the mechanisms which modulate intracellular calcium release and its spreading among astrocytes in the inflamed environment. Organotypic spinal cord slices are cultured for two or three weeks in vitro (WIV) and exposed for 6 h to a cocktail of cytokines (CKs), composed by tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1 ß) and granulocyte macrophage-colony stimulating factor (GM-CSF), or to lipopolysaccharide (LPS). By live calcium imaging of the ventral horn, we document an increase in active astrocytes and in the occurrence of spontaneous calcium oscillations displayed by these cells when exposed to each inflammatory threat. Through several pharmacological treatments, we demonstrate that intracellular calcium sources and the activation of connexin 43 (Cx43) hemichannels have a pivotal role in increasing calcium intercellular communication in both CKs and LPS conditions, while the Cx43 gap junction communication is apparently reduced by the inflammatory treatments.
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Astrocitos/fisiología , Señalización del Calcio/fisiología , Conexina 43/fisiología , Enfermedades Neuroinflamatorias/fisiopatología , Médula Espinal/fisiopatología , Animales , Células del Asta Anterior/fisiología , Citocinas/toxicidad , Vectores Genéticos/farmacología , Técnicas In Vitro , Microscopía Intravital , Lipopolisacáridos/toxicidad , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Enfermedades Neuroinflamatorias/inducido químicamente , Médula Espinal/embriologíaRESUMEN
INTRODUCTION/AIMS: It has been well established that spasticity interferes with smooth joint movements. Although the degree of spasticity is related to the excitability of anterior horn cells and is thought to improve after repetitive movements, the effect of the rhythm of repetitive movements on the excitability of anterior horn cells remains unknown. Therefore, we investigated the excitability of anterior horn cells after periodic and discrete repetitive movements using F waves. METHODS: Right-handed, healthy subjects were recruited for this study. Subjects then performed periodic or discrete repetitive thumb abduction movements for 10 seconds, measuring the F waves before, immediately after, and then 2 and 4 minutes after performing these movements. Specifically, the F waves were recorded from the abductor pollicis brevis muscle, after median nerve stimulation at the wrist. Next, the F/M amplitude ratio, which was used to evaluate the excitability of anterior horn cells, was compared before, immediately after, and 2 and 4 minutes after each task. RESULTS: A total of 12 subjects participated in this study. In the periodic task, the F/M amplitude ratio was found to be significantly decreased immediately after the task compared with before the task, but there was no significant difference between the other trials. Conversely, in the discrete task, there was no significant difference in the F/M amplitude ratio between trials. DISCUSSION: Periodic repetitive movements were found to temporarily reduce the excitability of anterior horn cells.
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Células del Asta Anterior , Músculo Esquelético , Células del Asta Anterior/fisiología , Potenciales Evocados Motores/fisiología , Mano , Humanos , Nervio Mediano/fisiología , Movimiento/fisiología , Músculo Esquelético/fisiologíaRESUMEN
The ability to sense and move within an environment are complex functions necessary for the survival of nearly all species. The spinal cord is both the initial entry site for peripheral information and the final output site for motor response, placing spinal circuits as paramount in mediating sensory responses and coordinating movement. This is partly accomplished through the activation of complex spinal microcircuits that gate afferent signals to filter extraneous stimuli from various sensory modalities and determine which signals are transmitted to higher order structures in the CNS and to spinal motor pathways. A mechanistic understanding of how inhibitory interneurons are organized and employed within the spinal cord will provide potential access points for therapeutics targeting inhibitory deficits underlying various pathologies including sensory and movement disorders. Recent studies using transgenic manipulations, neurochemical profiling, and single-cell transcriptomics have identified distinct populations of inhibitory interneurons which express an array of genetic and/or neurochemical markers that constitute functional microcircuits. In this review, we provide an overview of identified neural components that make up inhibitory microcircuits within the dorsal and ventral spinal cord and highlight the importance of inhibitory control of sensorimotor pathways at the spinal level.
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Vías Aferentes/fisiología , Interneuronas/fisiología , Movimiento/fisiología , Inhibición Neural/fisiología , Sensación/fisiología , Filtrado Sensorial/fisiología , Médula Espinal/citología , Animales , Células del Asta Anterior/química , Células del Asta Anterior/clasificación , Células del Asta Anterior/fisiología , Humanos , Interneuronas/química , Interneuronas/clasificación , Modelos Neurológicos , Neuronas Motoras/fisiología , Trastornos del Movimiento/fisiopatología , Fibras Nerviosas/fisiología , Proteínas del Tejido Nervioso/análisis , Neuropéptidos/análisis , Células del Asta Posterior/química , Células del Asta Posterior/clasificación , Trastornos de la Sensación/fisiopatología , Células Receptoras Sensoriales/fisiología , Médula Espinal/fisiología , Sinapsis/fisiologíaRESUMEN
Hyper-reflexia is occasionally seen in acute motor axonal neuropathy (AMAN), but its pathophysiology is unclear. We report a patient with AMAN following Campylobacter jejuni enteritis, who showed generalized hyper-reflexia, bilateral Hoffmann sign and right Babinski sign. MRI and transcranial magnetic stimulation of the motor cortex disclosed no corticospinal tract involvement. An extensive electrophysiological investigation documented α-motoneuron hyperexcitability and dysfunction of the interneuronal inhibitory circuits in the spinal anterior horn. We propose an immune-mediated damage of the spinal inhibitory interneuronal network as possible mechanism inducing hyper-reflexia in AMAN.
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Células del Asta Anterior/fisiología , Infecciones por Campylobacter/complicaciones , Síndrome de Guillain-Barré/fisiopatología , Reflejo Anormal/fisiología , Adulto , Potenciales Evocados Motores , Femenino , Síndrome de Guillain-Barré/etiología , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiopatología , Conducción Nerviosa , Reflejo Anormal/inmunología , Estimulación Magnética TranscranealRESUMEN
The significance of activated microglia around motoneurons axotomized after nerve injuries has been intensely debated. In particular, whether microglia become phagocytic is controversial. To resolve these issues we directly observed microglia behaviors with two-photon microscopy in ex vivo spinal cord slices from CX3CR1-GFP mice complemented with confocal analyses of CD68 protein. Axotomized motoneurons were retrogradely-labeled from muscle before nerve injuries. Microglia behaviors close to axotomized motoneurons greatly differ from those within uninjured motor pools. They develop a phagocytic phenotype as early as 3 days after injury, characterized by frequent phagocytic cups, high phagosome content and CD68 upregulation. Interactions between microglia and motoneurons changed with time after axotomy. Microglia first extend processes that end in phagocytic cups at the motoneuron surface, then they closely attach to the motoneuron while extending filopodia over the cell body. Confocal 3D analyses revealed increased microglia coverage of the motoneuron cell body surface with time after injury and the presence of CD68 granules in microglia surfaces opposed to motoneurons. Some microglia formed macroclusters associated with dying motoneurons. Microglia in these clusters display the highest CD68 expression and associate with cytotoxic T-cells. These observations are discussed in relation to current theories on microglia function around axotomized motoneurons.
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Comunicación Celular/fisiología , Microglía/fisiología , Neuronas Motoras/fisiología , Traumatismos de los Nervios Periféricos/patología , Animales , Células del Asta Anterior/fisiología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Axotomía , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neuroprotección/fisiología , Médula Espinal/anatomía & histología , Médula Espinal/diagnóstico por imagen , Linfocitos T Citotóxicos/metabolismoRESUMEN
We develop magnetic resonance (MR) methods for real-time measurement of tissue microstructure and membrane permeability of live and fixed excised neonatal mouse spinal cords. Diffusion and exchange MR measurements are performed using the strong static gradient produced by a single-sided permanent magnet. Using tissue delipidation methods, we show that water diffusion is restricted solely by lipid membranes. Most of the diffusion signal can be assigned to water in tissue which is far from membranes. The remaining 25% can be assigned to water restricted on length scales of roughly a micron or less, near or within membrane structures at the cellular, organelle, and vesicle levels. Diffusion exchange spectroscopy measures water exchanging between membrane structures and free environments at 100 s-1.
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Membrana Celular/ultraestructura , Imagen de Difusión por Resonancia Magnética/métodos , Membranas Intracelulares/ultraestructura , Espectroscopía de Resonancia Magnética/métodos , Médula Espinal/ultraestructura , Potenciales de Acción , Animales , Animales Recién Nacidos , Anisotropía , Células del Asta Anterior/fisiología , Agua Corporal , Detergentes/farmacología , Deuterio , Difusión , Imagen de Difusión por Resonancia Magnética/instrumentación , Diseño de Equipo , Espectroscopía de Resonancia Magnética/instrumentación , Lípidos de la Membrana/química , Ratones , Movimiento (Física) , Octoxinol/farmacología , Médula Espinal/efectos de los fármacosRESUMEN
Implantable spinal-cord-neuroprostheses aiming to restore standing and walking after paralysis have been extensively studied in animal models (mainly cats) and have shown promising outcomes. This study aimed to take a critical step along the clinical translation path of these neuroprostheses, and investigated the organization of the neural networks targeted by these implants in a non-human primate. This was accomplished by advancing a microelectrode into various locations of the lumbar enlargement of the spinal cord, targeting the ventral horn of the gray matter. Microstimulation in these locations produced a variety of functional movements in the hindlimb. The resulting functional map of the spinal cord in monkeys was found to have a similar overall organization along the length of the spinal cord to that in cats. This suggests that the human spinal cord may also be organized similarly. The obtained spinal cord maps in monkeys provide important knowledge that will guide the very first testing of these implants in humans.
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Estimulación Eléctrica/métodos , Neuroestimuladores Implantables/tendencias , Región Lumbosacra/fisiología , Animales , Células del Asta Anterior/fisiología , Miembro Posterior/fisiología , Macaca mulatta/fisiología , Microelectrodos , Movimiento/fisiología , Prótesis Neurales/tendencias , Parálisis/fisiopatología , Primates/fisiología , Médula Espinal/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Caminata/fisiologíaRESUMEN
During fast movements in vertebrates, slow motor units are thought to be deactivated due to the mechanical demands of muscle contraction, but the associated neuronal mechanisms for this are unknown. Here, we perform functional analyses of spinal V1 neurons by selectively killing them in larval zebrafish, revealing two functions of V1 neurons. The first is the long-proposed role of V1 neurons: they play an important role in shortening the cycle period during swimming by providing in-phase inhibition. The second is that V1 neurons play an important role in the selection of active sets of neurons. We show that strong inhibitory inputs coming from V1 neurons play a crucial role in suppressing the activities of slow-type V2a and motor neurons, and, consequently, of slow muscles during fast swimming. Our results thus highlight the critical role of spinal inhibitory neurons for silencing slow-component neurons during fast movements.
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Células del Asta Anterior/fisiología , Células de Renshaw/fisiología , Natación/fisiología , Animales , Animales Modificados Genéticamente , Embrión no Mamífero , Larva , Modelos Animales , Pez CebraRESUMEN
C-type synaptic boutons (C-boutons) provide cholinergic afferent input to spinal cord motor neurons (MNs), which display an endoplasmic reticulum (ER)-related subsurface cistern (SSC) adjacent to their postsynaptic membrane. A constellation of postsynaptic proteins is clustered at C-boutons, including M2 muscarinic receptors, potassium channels, and σ-1 receptors. In addition, we previously found that neuregulin (NRG)1 is associated with C-boutons at postsynaptic SSCs, whereas its ErbB receptors are located in the presynaptic compartment. C-bouton-mediated regulation of MN excitability has been implicated in MN disease, but NRG1-mediated functions and the impact of various pathologic conditions on C-bouton integrity have not been studied in detail. Here, we investigated changes in C-boutons after electrical stimulation, pharmacological treatment, and peripheral nerve axotomy. SSC-linked NRG1 clusters were severely disrupted in acutely stressed MNs and after tunicamycin-induced ER stress. In axotomized MNs, C-bouton loss occurred in concomitance with microglial recruitment and was prevented by the ER stress inhibitor salubrinal. Activated microglia displayed a positive chemotaxis to C-boutons. Analysis of transgenic mice overexpressing NRG1 type I and type III isoforms in MNs indicated that NRG1 type III acts as an organizer of SSC-like structures, whereas NRG1 type I promotes synaptogenesis of presynaptic cholinergic terminals. Moreover, MN-derived NRG1 signals may regulate the activity of perineuronal microglial cells. Together, these data provide new insights into the molecular and cellular pathology of C-boutons in MN injury and suggest that distinct NRG1 isoform-mediated signaling functions regulate the complex matching between pre- and postsynaptic C-bouton elements.-Salvany, S., Casanovas, A., Tarabal, O., Piedrafita, L., Hernández, S., Santafé, M., Soto-Bernardini, M. C., Calderó, J., Schwab, M. H., Esquerda, J. E. Localization and dynamic changes of neuregulin-1 at C-type synaptic boutons in association with motor neuron injury and repair.
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Células del Asta Anterior/fisiología , Fibras Nerviosas Amielínicas/fisiología , Regeneración Nerviosa/fisiología , Neurregulina-1/fisiología , Terminales Presinápticos/fisiología , Nervio Ciático/lesiones , Animales , Axotomía , Fibras Colinérgicas/fisiología , Cinamatos/farmacología , Estimulación Eléctrica , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/fisiología , Retículo Endoplásmico Liso/fisiología , Retículo Endoplásmico Liso/ultraestructura , Ratones , Ratones Transgénicos , Microglía/fisiología , Compresión Nerviosa , Neurregulina-1/genética , Terminales Presinápticos/efectos de los fármacos , Isoformas de Proteínas/fisiología , Nervio Ciático/fisiología , Transducción de Señal/fisiología , Fracciones Subcelulares/química , Tiourea/análogos & derivados , Tiourea/farmacología , Tunicamicina/toxicidad , Vacuolas/metabolismo , Vacuolas/ultraestructuraRESUMEN
PURPOSE: Motor imagery, the process of imagining a physical action, has been shown to facilitate the excitability of spinal anterior horn cells. In the acute phase after a stroke, the excitability of spinal anterior horn cells is significantly reduced, which leads to motor deficits. This loss of movement can be prevented by increasing the excitability of spinal anterior horn cells immediately following an injury. Motor imagery is an effective method for facilitating the excitability of spinal anterior horn cells in patients with impaired movement; however, the optimal duration for motor imagery is unclear. MATERIALS AND METHODS: To investigate time-dependent changes in spinal anterior horn cell excitability during motor imagery, healthy adult participants were recruited to measure the F-wave, an indicator of anterior horn cell excitability. F-waves were measured from participants at baseline, during motor imagery, and post-motor imagery. During motor imagery, participants imagined isometric thenar muscle activity at 50% maximum voluntary contraction for 5 min. F-waves were measured at 1, 3, and 5 min after beginning motor imagery and analysed for persistence and F/M amplitude ratio. RESULTS: Persistence and F/M amplitude ratios at 1- and 3-min after motor imagery initiation were significantly greater than at baseline. The persistence and F/M amplitude ratio at 5-min after motor imagery initiation, however, was comparable to baseline levels. CONCLUSION: Therefore, 1 to 3 min of motor imagery is likely sufficient to facilitate the excitability of spinal anterior horn cells.
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Células del Asta Anterior/fisiología , Potenciales Evocados Motores/fisiología , Imaginación/fisiología , Músculo Esquelético/fisiología , Adulto , Electroencefalografía , Electromiografía , Femenino , Voluntarios Sanos , Humanos , Masculino , Tiempo de Reacción/fisiología , Estadísticas no Paramétricas , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Interactions between motoneurons and glial cells are pivotal to regulate and maintain functional states and synaptic connectivity in the spinal cord. In vivo two-photon imaging of the nervous system provided novel and unexpected knowledge about structural and physiological changes in the grey matter of the forebrain and in the dorsal white matter of the spinal cord. NEW METHOD: Here, we describe a novel experimental strategy to investigate the spinal grey matter, i.e. the ventral horn motoneurons and their adjacent glial cells by employing in vivo two-photon laser-scanning microscopy (2P-LSM) in anesthetized transgenic mice. RESULTS: After retrograde tracer labelling in transgenic mice with cell-specific expression of fluorescent proteins and surgical exposure of the lumbar intumescence groups of motoneurons could be visualized deeply localized in the ventral horn. In this region, morphological responses of microglial cells to ATP could be recorded for an hour. In addition, using in mice with expression of GCaMP3 in astrocytes, physiological Ca2+ signals could be recorded after local noradrenalin application. COMPARISON WITH EXISTING METHODS: Previous in vivo imaging protocols were restricted to the superficial dorsal white matter or upper layers of the dorsal horn. Here, we modified a multi-step procedure originally established for a root-crush injury. We adapted it to simultaneously visualize motoneurons and adjacent glial cells in living animals. CONCLUSION: A modified surgery approach is presented to visualize fluorescently labelled motoneurons and glial cells at a depth of more than 200⯵m in the grey matter ventral horn of the mouse spinal cord.
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Células del Asta Anterior/fisiología , Neuronas Motoras/fisiología , Neuroglía/fisiología , Imagen Óptica/métodos , Animales , Células del Asta Anterior/citología , Técnica del Anticuerpo Fluorescente/métodos , Sustancia Gris/citología , Sustancia Gris/fisiología , Ratones Transgénicos , Microscopía Confocal , Neuronas Motoras/citología , Neuroglía/citología , Asta Ventral de la Médula Espinal/cirugíaRESUMEN
Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.
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Neuronas Motoras/patología , Neuronas Motoras/fisiología , Músculo Esquelético/patología , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatología , Cola (estructura animal)/inervación , Animales , Células del Asta Anterior/metabolismo , Células del Asta Anterior/patología , Células del Asta Anterior/fisiología , Estimulación Eléctrica , Electroacupuntura , Femenino , Neuronas Motoras/metabolismo , Atrofia Muscular , Neurotrofina 3/metabolismo , Ratas Sprague-Dawley , Médula Espinal , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapiaRESUMEN
Motoneuron degeneration is the hallmark of amyotrophic lateral sclerosis (ALS). The cause and predisposing factors for sporadic ALS are still unknown. Exposure to a specific environmental risk factors in subjects with a susceptibility genotype may increase the risk of the disease. The role of physical activity and the use of anabolic steroids are still debated in epidemiological studies on patients and murine models of ALS. To assess at the cellular level the role (beneficial or detrimental) of physical exercise and the use of anabolic steroid, we here investigated, in SOD1(G93A) (mSOD1) mice and wild-type littermates, changes in the ventral horn after regular exercise, treatment with the anabolic androgenic steroid 19-nortestosterone (nandrolone), and their combination, compared with matched control sedentary mice. The experiments were pursued for several weeks until symptom onset in mSOD1 mice. Lumbar motoneurons, astrocytes and microglia were analyzed. In wild-type mice, cytological alterations of motoneurons were observed especially after nandrolone treatment. The following main findings were observed in treated mSOD1 mice versus untreated ones: i) nandrolone treatment markedly enhanced motoneuron loss; this detrimental effect was reverted by the combination with exercise, resulting in increased motoneuron survival; ii) astrocytic activation was most marked after nandrolone treatment when motoneuron damage was most severe; iii) microglia activation was most marked after physical exercise when motoneuron damage was less severe. The results indicate a vulnerability of mSOD1 motoneurons to nandrolone treatment, a potential neuroprotective effect of physical exercise, and a modulation by glial cells in the ALS murine model in the examined paradigms.
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Esclerosis Amiotrófica Lateral/terapia , Anabolizantes/farmacología , Células del Asta Anterior/fisiología , Terapia por Ejercicio , Nandrolona/farmacología , Neuroglía/fisiología , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/fisiopatología , Anabolizantes/toxicidad , Animales , Células del Asta Anterior/efectos de los fármacos , Células del Asta Anterior/patología , Peso Corporal , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Colina O-Acetiltransferasa/metabolismo , Modelos Animales de Enfermedad , Vértebras Lumbares , Masculino , Ratones Transgénicos , Nandrolona/toxicidad , Neuroglía/efectos de los fármacos , Neuroglía/patología , Distribución Aleatoria , Carrera/fisiología , Conducta SedentariaRESUMEN
The motor unit comprises the anterior horn cell, its axon, and the muscle fibers that it innervates. Although the true number of motor units is unknown, the number of motor units appears to vary greatly between different muscles and between different individuals. Assessment of the number and function of motor units is needed in diseases of the anterior horn cell and other motor nerve disorders. Amyotrophic lateral sclerosis is the most important disease of anterior horn cells. The need for an effective biomarker for assessing disease progression and for use in clinical trials in amyotrophic lateral sclerosis has stimulated the study of methods to measure the number of motor units. Since 1970 a number of different methods, including the incremental, F-wave, multipoint, and statistical methods, have been developed but none has achieved widespread applicability. Two methods (MUNIX and the multipoint incremental method) are in current use across multiple centres and are discussed in detail in this review, together with other recently published methods. Imaging with magnetic resonance and ultrasound is increasingly being applied to this area. Motor unit number estimates have also been applied to other neuromuscular diseases such as spinal muscular atrophy, compression neuropathies, and prior poliomyelitis. The need for an objective measure for the assessment of motor units remains tantalizingly close but unfulfilled in 2016.
Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/fisiopatología , Células del Asta Anterior/fisiología , Músculo Esquelético/fisiopatología , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/fisiopatología , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Biomarcadores , Progresión de la Enfermedad , Estimulación Eléctrica , Electromiografía , Humanos , Imagen por Resonancia Magnética , Conducción Nerviosa , Enfermedades Neuromusculares/diagnóstico por imagen , UltrasonografíaRESUMEN
Hydrogen peroxide (H2O2), a reactive oxygen species, is an important signaling molecule for synaptic and neuronal activity in the central nervous system; it is produced excessively in brain ischemia and spinal cord injury. Although H2O2-mediated modulations of synaptic transmission have been reported in ventral horn (VH) neurons of the rat spinal cord, the effects of H2O2 on neuronal excitability and membrane properties remain poorly understood. Accordingly, the present study investigated such effects using a whole-cell patch-clamp technique. The bath-application of H2O2 decreased neuronal excitability accompanied by decreased input resistance, firing frequency, and action potential amplitude and by increased rheobase. These H2O2-mediated changes were induced by activation of extrasynaptic, but not synaptic, GABAA receptors. Indeed, GABAergic tonic currents were enhanced by H2O2. On the other hand, the amplitude of medium and slow afterhyperpolarization (mAHP and sAHP), which plays important roles in controlling neuronal excitability and is mediated by small-conductance calcium-activated potassium (SK) channels, was significantly decreased by H2O2. When extrasynaptic GABAA receptors were completely blocked, these decreases of mAHP and sAHP persisted, and H2O2 increased excitability, suggesting that H2O2 per se might have the potential to increase neuronal excitability via decreased SK channel conductance. These findings indicate that activating extrasynaptic GABAA receptors or SK channels may attenuate acute neuronal damage caused by H2O2-induced hyperexcitability and therefore represent a novel therapeutic target for the prevention and treatment of H2O2-induced motor neuron disorders.
Asunto(s)
Células del Asta Anterior/fisiología , Peróxido de Hidrógeno/metabolismo , Potenciales de la Membrana/fisiología , Animales , Células del Asta Anterior/efectos de los fármacos , Bicuculina/farmacología , Relación Dosis-Respuesta a Droga , Peróxido de Hidrógeno/farmacología , Potenciales de la Membrana/efectos de los fármacos , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Neurotransmisores/farmacología , Técnicas de Placa-Clamp , Ratas Wistar , Receptores de GABA-A/metabolismo , Receptores de Glicina/metabolismo , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Estricnina/farmacología , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Técnicas de Cultivo de Tejidos , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that selectively affects the motor neurons. The details of the mechanisms of selective motor-neuron death remain unknown and no effective therapy has been developed. We investigated the therapy with bone-marrow mononuclear cells (BMMC) in a mouse model of ALS (SOD1(G93A) mice). METHODS: We injected 10(6) BMMC into the lumbar portion of the spinal cord of SOD1(G93A) mice in presymptomatic (9 weeks old) and symptomatic (14 weeks old) phases. In each condition, we analyzed the progression of disease and the lifespan of the animals. RESULTS: We observed a mild transitory delay in the disease progression in the animals injected with BMMC in the presymptomatic phase. However, we observed no increase in the lifespan. When we injected BMMC in the symptomatic phase, we observed no difference in the animals' lifespan or in the disease progression. Immunohistochemistry for NeuN showed a decrease in the number of motor neurons during the course of the disease, and this decrease was not affected by either treatment. Using different strategies to track the BMMC, we noted that few cells remained in the spinal cord after transplantation. This observation could explain why the BMMC therapy had only a transitory effect. CONCLUSION: This is the first report of intraspinal BMMC therapy in a mouse model of ALS. We conclude this cellular therapy has only a mild transitory effect when performed in the presymptomatic phase of the disease.
Asunto(s)
Esclerosis Amiotrófica Lateral/terapia , Enfermedades Asintomáticas/terapia , Trasplante de Médula Ósea , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Células del Asta Anterior/fisiología , Movimiento Celular , Supervivencia Celular , Rastreo Celular , Femenino , Inyecciones Espinales , Región Lumbosacra/patología , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Microglía/fisiología , Actividad Motora , Mutación Missense , Recuperación de la Función , Superóxido Dismutasa/genética , Superóxido Dismutasa-1RESUMEN
OBJECTIVE: The Adamkiewicz artery (AKA) supplies pudendal nerve roots and conus medullaris. The aim of this study was to elucidate if there is any relationship between neurodegenerative changes of the Onuf nucleus (ON)-pudendal nerve ganglia complex secondary to vasospasm of the AKA after spinal subarachnoid hemorrhage (SAH). METHODS: This study was conducted on 22 rabbits, which were randomly divided into 3 groups: control (n = 5), sham (n = 5), and spinal SAH (n = 12). Experimental spinal SAH was induced at the L2 level. After 2 weeks, the ON-pudendal nerve ganglia complex and AKA were examined histopathologically. Bladder volume values were estimated, and results were analyzed statistically. RESULTS: Two animals died within the first week of experiment. Histopathologically, severe vasospasm of the AKA and neuronal degeneration and neuronal apoptosis were observed in the ON-pudendal nerve ganglia complex in 5 animals of the SAH group. The mean volume of the imaginary AKA, mean bladder volumes, and degenerated neuron densities of ON and pudendal nerve ganglia were estimated. We found that vasospasm of the AKA led to numerous neuron degenerations in ON and pudendal ganglia and consequently urinary retention (P < 0.005). CONCLUSIONS: ON-pudendal nerve ganglia complex degeneration secondary to vasospasm of the AKA may be a cause of urinary retention after spinal SAH.