scholarly journals Third-Degree Hindpaw Burn Injury Induced Apoptosis of Lumbar Spinal Cord Ventral Horn Motor Neurons and Sciatic Nerve and Muscle Atrophy in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Sheng-Hua Wu ◽  
Shu-Hung Huang ◽  
Kuang-I Cheng ◽  
Chee-Yin Chai ◽  
Jwu-Lai Yeh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Motor Neurons ◽  
Gastrocnemius Muscle ◽  
Muscle Wasting ◽  
Burn Injury ◽  
Ventral Horn ◽  
Denervation Atrophy ◽  
Lumbar Spinal ◽  
Gastrocnemius Muscles

Background. Severe burns result in hypercatabolic state and concomitant muscle atrophy that persists for several months, thereby limiting patient recovery. However, the effects of burns on the corresponding spinal dermatome remain unknown. This study aimed to investigate whether burns induce apoptosis of spinal cord ventral horn motor neurons (VHMNs) and consequently cause skeletal muscle wasting.Methods. Third-degree hindpaw burn injury with 1% total body surface area (TBSA) rats were euthanized 4 and 8 weeks after burn injury. The apoptosis profiles in the ventral horns of the lumbar spinal cords, sciatic nerves, and gastrocnemius muscles were examined. The Schwann cells in the sciatic nerve were marked with S100. The gastrocnemius muscles were harvested to measure the denervation atrophy.Result. The VHMNs apoptosis in the spinal cord was observed after inducing third-degree burns in the hindpaw. The S100 and TUNEL double-positive cells in the sciatic nerve increased significantly after the burn injury. Gastrocnemius muscle apoptosis and denervation atrophy area increased significantly after the burn injury.Conclusion. Local hindpaw burn induces apoptosis in VHMNs and Schwann cells in sciatic nerve, which causes corresponding gastrocnemius muscle denervation atrophy. Our results provided an animal model to evaluate burn-induced muscle wasting, and elucidate the underlying mechanisms.

scholarly journals Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection

2019 ◽  
Vol 33 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Kazu Kobayakawa ◽  
Kyleigh Alexis DePetro ◽  
Hui Zhong ◽  
Bau Pham ◽  
Masamitsu Hara ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Ventral Horn ◽  
Lumbar Spinal Cord ◽  
Locomotor Training ◽  
Synaptic Structure ◽  
Cord Injury ◽  
Lumbar Spinal ◽  
Spinal Cord Hemisection ◽  
Activity Dependent

Background. We previously demonstrated that step training leads to reorganization of neuronal networks in the lumbar spinal cord of rodents after a hemisection (HX) injury and step training, including increases excitability of spinally evoked potentials in hindlimb motor neurons. Methods. In this study, we investigated changes in RNA expression and synapse number using RNA-Seq and immunohistochemistry of the lumbar spinal cord 23 days after a mid-thoracic HX in rats with and without post-HX step training. Results. Gene Ontology (GO) term clustering demonstrated that expression levels of 36 synapse-related genes were increased in trained compared with nontrained rats. Many synaptic genes were upregulated in trained rats, but Lrrc4 (coding NGL-2) was the most highly expressed in the lumbar spinal cord caudal to the HX lesion. Trained rats also had a higher number of NGL-2/synaptophysin synaptic puncta in the lumbar ventral horn. Conclusions. Our findings demonstrate clear activity-dependent regulation of synapse-related gene expression post-HX. This effect is consistent with the concept that activity-dependent phenomena can provide a mechanistic drive for epigenetic neuronal group selection in the shaping of the reorganization of synaptic networks to learn the locomotion task being trained after spinal cord injury.

Autologous adipose-derived stem cells attenuate muscular atrophy and protect spinal cord ventral horn motor neurons in an animal model of burn injury

Cytotherapy ◽  
2015 ◽  
Vol 17 (8) ◽  
pp. 1066-1075 ◽  
Author(s):  
Sheng-Hua Wu ◽  
Shu-Hung Huang ◽  
Yi-Ching Lo ◽  
Chee-Yin Chai ◽  
Su-Shin Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Animal Model ◽  
Motor Neurons ◽  
Burn Injury ◽  
Muscular Atrophy ◽  
Ventral Horn ◽  
Adipose Derived Stem Cells

scholarly journals Localized Induction of Wild-Type and Mutant Alpha-Synuclein Aggregation Reveals Propagation along Neuroanatomical Tracts

2018 ◽  
Vol 92 (18) ◽  
Author(s):  
Jacob I. Ayers ◽  
Cara J. Riffe ◽  
Zachary A. Sorrentino ◽  
Jeffrey Diamond ◽  
Eric Fagerli ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Prion Protein ◽  
Motor Neurons ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Lumbar Spinal Cord ◽  
The Central Nervous System ◽  
Lumbar Spinal ◽  
Alpha Synuclein Aggregation

ABSTRACTMisfolded alpha-synuclein (αS) may exhibit a number of characteristics similar to those of the prion protein, including the apparent ability to spread along neuroanatomical connections. The demonstration for this mechanism of spread is largely based on the intracerebral injections of preaggregated αS seeds in mice, in which it cannot be excluded that diffuse, surgical perturbations and hematogenous spread also contribute to the propagation of pathology. For this reason, we have utilized the sciatic nerve as a route of injection to force the inoculum into the lumbar spinal cord and induce a localized site for the onset of αS inclusion pathology. Our results demonstrate that mouse αS fibrils (fibs) injected unilaterally in the sciatic nerve are efficient in inducing pathology and the onset of paralytic symptoms in both the M83 and M20 lines of αS transgenic mice. In addition, a spatiotemporal study of these injections revealed a predictable spread of pathology to brain regions whose axons synapse directly on ventral motor neurons in the spinal cord, strongly supporting axonal transport as a mechanism of spread of the αS inducing, or seeding, factor. We also revealed a relatively decreased efficiency for human αS fibs containing the E46K mutation to induce disease via this injection paradigm, supportive of recent studies demonstrating a diminished ability of this mutant αS to undergo aggregate induction. These results further demonstrate prion-like properties for αS by the ability for a progression and spread of αS inclusion pathology along neuroanatomical connections.IMPORTANCEThe accumulation of alpha-synuclein (αS) inclusions is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Recently, a number of studies have demonstrated similarities between the prion protein and αS, including its ability to spread along neuroanatomical tracts throughout the central nervous system (CNS). However, there are caveats in each of these studies in which the injection routes used had the potential to result in a widespread dissemination of the αS-containing inocula, making it difficult to precisely define the mechanisms of spread. In this study, we assessed the spread of pathology following a localized induction of αS inclusions in the lumbar spinal cord following a unilateral injection in the sciatic nerve. Using this paradigm, we demonstrated the ability for αS inclusion spread and/or induction along neuroanatomical tracts within the CNS of two αS-overexpressing mouse models.

scholarly journals Identification of 17 highly expressed genes within mouse lumbar spinal cord anterior horn region from an in-situ hybridization atlas of 3430 genes: implications for motor neuron disease

2014 ◽  
Vol 6 (2) ◽  
Author(s):  
Michael A. Meyer
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Ventral Horn ◽  
Janus Kinase ◽  
Anterior Horn ◽  
Lumbar Spinal Cord ◽  
Spinal Motor ◽  
Lumbar Spinal

In an effort to find possible new gene candidates involved in the causation of amyotrophic lateral sclerosis (ALS), a prior version of the on-line brain gene expression atlas GENSAT was extensively searched for selectively intense expression within spinal motor neurons. Using autoradiographic data of <em>in</em>-<em>situ</em> hybridization from 3430 genes, a search for selectively intense activity was made for the anterior horn region of murine lumbar spinal cord sectioned in the axial plane. Of 3430 genes, a group of 17 genes was found to be highly expressed within the anterior horn suggesting localization to its primary cellular constituent, the alpha spinal motor neuron. For some genes, an inter-relationship to ALS was already known, such as for heavy, medium, and light neurofilaments, and peripherin. Other genes identified include: <em>Gamma Synuclein, GDNF, SEMA3A, Extended Synaptotagmin-like protein 1, LYNX1, HSPA12a, Cadherin 22, PRKACA, TPPP3</em> as well as <em>Choline Acetyltransferase, Janus Kinase 1</em>, and the<em> Motor Neuron</em> and <em>Pancreas Homeobox 1</em>. Based on this study, <em>Fibroblast Growth Factor 1</em> was found to have a particularly selective and intense localization pattern to the ventral horn and may be a good target for development of motor neuron disease therapies; further research is needed.

scholarly journals Co-injection of wheat germ agglutinin-HRP and choleragenoid-HRP into the sciatic nerve of the rat blocks transganglionic transport.

1995 ◽  
Vol 43 (5) ◽  
pp. 489-495 ◽  
Author(s):  
H Liu ◽  
I J Llewellyn-Smith ◽  
A I Basbaum
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Motor Neurons ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Lumbar Spinal Cord ◽  
Retrograde Labeling ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Lumbar Spinal

We report on the surprising loss of transganglionic and retrograde labeling in the spinal cord of the rat after co-injection of the tracers wheat germ agglutinin-HRP (WGA-HRP) and choleragenoid toxin-HRP (CTB-HRP) into the sciatic nerve. Injection of WGA-HRP alone produced a pattern of transganglionic label consistent with transport by small-diameter primary afferent fibers. Small cell bodies were labeled in the ipsilateral dorsal root ganglion (DRG) and there was dense terminal labeling in the superficial dorsal horn of the lumbar spinal cord. Injection of CTB-HRP alone produced a pattern of transganglionic labeling consistent with transport by large-diameter primary afferent fibers. Large cell bodies were labeled in the DRG and there was dense terminal labeling in the nucleus proprius (Laminae III-V) in the spinal cord. CTB-HRP also produced extensive retrograde labeling of ventral horn motor neurons. When the two tracers were co-injected, we found few labeled cells in the ipsilateral DRG and there was almost complete loss of transganglionic terminal labeling in the lumbar spinal cord. Retrograde labeling of motor neurons was also significantly reduced. Even when one of the tracers (e.g., WGA-HRP) was injected 24 hr after and up to 10 mm proximal to the site of the first tracer (e.g., CTB-HRP), an inhibitory interaction was detected. The labeling pattern was always characteristic of the first tracer injected.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in serotonin-induced potentials during spinal cord development

1993 ◽  
Vol 69 (4) ◽  
pp. 1338-1349 ◽  
Author(s):  
L. Ziskind-Conhaim ◽  
B. S. Seebach ◽  
B. X. Gao
Keyword(s):  
Spinal Cord ◽  
Direct Action ◽  
Membrane Resistance ◽  
Ventral Horn ◽  
Repetitive Firing ◽  
Lumbar Spinal Cord ◽  
Receptor Subtypes ◽  
Gamma Aminobutyric Acid ◽  
Spinal Neurons ◽  
Lumbar Spinal

1. Motoneuron responses to serotonin (5-hydroxytryptamine, 5-HT), and the growth pattern of 5-HT projections into the ventral horn were studied in the isolated spinal cord of embryonic and neonatal rats. 2. 5-HT projections first appeared in lumbar spinal cord at days 16-17 of gestation (E16-E17) and were localized in the lateral and ventral funiculi. By E18, the projections had grown into the ventral horn, and at 1-2 days after birth they were in close apposition to motoneuron somata. 3. At E16-E17, slow-rising depolarizing potentials of 1-4 mV were recorded intracellularly in lumbar motoneurons in response to bath application of 5-HT. These potentials were not apparent after E18; at that time 5-HT generated long-lasting depolarizations with an average amplitude of 6 mV, and an increase of 11% in membrane resistance. Starting at E18, 5-HT also induced high-frequency fast-rising potentials that were blocked by antagonists of glutamate, gamma-aminobutyric acid, and glycine. 4. Motoneuron responses to 5-HT increased significantly after birth, when 5-HT produced an average depolarization of 19 mV and repetitive firing of action potentials. 5. Tetrodotoxin and high Mg2+ did not reduce the amplitude of the long-lasting depolarizations, which suggested that they were produced by direct action of 5-HT on motoneuron membrane. 6. At all developmental ages, 5-HT reduced the amplitude of dorsal root-evoked potentials. The suppressed responses were neither due to 5-HT-induced depolarization nor the result of a decrease in motoneuron excitability. 7. The pharmacological profile of 5-HT-induced potentials was studied with the use of various agonists and antagonists of 5-HT. The findings indicated that the actions of 5-HT on spinal neurons were mediated via multiple 5-HT receptor subtypes. 8. Our results suggested that 5-HT excited spinal neurons before 5-HT projections grew into the ventral horn. The characteristics of 5-HT-induced potentials changed, however, at the time when the density of 5-HT projections increased in the motor nuclei.

Noradrenergic synapses and effects of noradrenaline on interneurons in the ventral horn of the cat spinal cord

1977 ◽  
Vol 55 (3) ◽  
pp. 399-412 ◽  
Author(s):  
Larry M. Jordan ◽  
David A. McCrea ◽  
John D. Steeves ◽  
John E. Menzies
Keyword(s):  
Spinal Cord ◽  
Close Contact ◽  
Cell Types ◽  
Muscle Afferents ◽  
Ventral Horn ◽  
Lumbar Spinal Cord ◽  
High Threshold ◽  
Depressant Action ◽  
Motor Nuclei ◽  
Lumbar Spinal

Histochemical and electrophysiological procedures were carried out to determine the cell types in the ventral horn which are in close contact with noradrenergic terminals and to identify the types of neurons in the ventral horn which are influenced by noradrenaline (NA). Fluorescence histochemical studies revealed that noradrenaline-containing fibers rarely form intimate contacts with alpha motoneurons, whereas many small interneurons which are closely invested with fluorescent fibers can be found near the motoneurons. The effects of microiontophoretically applied NA on interneurons were examined in the lateral motor areas of the lumbar spinal cord ventral horn. NA had a substantial depressant action on 43% of cells in chloralose-anesthetized and decerebrate cats; it excited 6% of the cells, and was without effect on the rest. The cells which were depressed by NA could be excited by electrical stimulation of high threshold muscle afferents or skin afferents, and they could be influenced from a variety of exteroceptive and proprioceptive inputs. Owing to considerable convergence on the affected interneurons, no distinct population of NA-sensitive interneurons could be identified. Many of the interneurons strongly depressed by NA were found near the motor nuclei. The hypothesis is presented that inhibitory actions of NA on interneurons in the motor nuclei might explain its hyperpolarizing action on motoneurons.

scholarly journals Analysis of the Molecular Signaling Signatures of Muscle Protein Wasting Between the Intercostal Muscles and the Gastrocnemius Muscles in db/db Mice

2019 ◽  
Vol 20 (23) ◽  
pp. 6062 ◽  
Author(s):  
Kun Woo Kim ◽  
Mi-Ock Baek ◽  
Ji-Young Choi ◽  
Kuk Hui Son ◽  
Mee-Sup Yoon
Keyword(s):  
Gastrocnemius Muscle ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Respiratory Muscles ◽  
Diabetic Mouse ◽  
Molecular Signaling ◽  
Akt Phosphorylation ◽  
Intercostal Muscles ◽  
The Difference ◽  
Gastrocnemius Muscles

Type 2 diabetes (T2D) patients suffer from dyspnea, which contributes to disease-related morbidity. Although T2D has been reported to induce a catabolic state in skeletal muscle, whether T2D induces muscle wasting in respiratory muscles has not yet been investigated. In this study, we examine the difference in the molecular signaling signature of muscle wasting between the intercostal and gastrocnemius muscles using db/db mice, a well-known diabetic mouse model. Akt phosphorylation was significantly decreased in both the intercostal and gastrocnemius muscles of db/db mice and was accompanied by a decrease in mTORC1 activity. In addition, FoxO phosphorylation was suppressed, and ubiquitin-proteasome degradation, characterized by the level of Atrogin-1 and MuRF1, was subsequently enhanced in both muscle types of db/db mice. An increase in LC3BII levels and a decrease in p62 levels marked the occurrence of substantial autophagy in the gastrocnemius muscle but not in the intercostal muscles of db/db mice. Therefore, we suggest that the signaling events of muscle wasting in the intercostal muscles of db/db mice are different from those in the gastrocnemius muscle of db/db mice.

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