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 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.

Lasting paraplegia caused by loss of lumbar spinal cord interneurons in rats: no direct correlation with motor neuron loss

2000 ◽  
Vol 93 (2) ◽  
pp. 266-275 ◽  
Author(s):  
Bassam Hadi ◽  
Y. Ping Zhang ◽  
Darlene A. Burke ◽  
Christopher B. Shields ◽  
David S. K. Magnuson
Keyword(s):  
Spinal Cord ◽  
Locomotor Activity ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Lumbar Spinal Cord ◽  
Neuron Loss ◽  
Content Type ◽  
Motor Neuron Loss ◽  
Lumbar Spinal ◽  
Fine Print

Object. The aims of this study were to investigate further the role played by lumbar spinal cord interneurons in the generation of locomotor activity and to develop a model of spinal cord injury suitable for testing neuron replacement strategies. Methods. Adult rats received intraspinal injections of kainic acid (KA). Locomotion was assessed weekly for 4 weeks by using the Basso, Beattie, and Bresnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor evoked potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscles at 1 and 4 weeks. No changes in transcranial MMEP latency were noted following KA injection, indicating that the descending motor pathways responsible for these responses, including the alpha motor neurons, were not compromised. Rats in which KA injections included much of the L-2 segment (10 animals) showed severe locomotor deficits, with a mean BBB score of 4.5 ± 3.6 (± standard deviation). Rats that received lesions rostral to the L-2 segment (four animals) were able to locomote and had a mean BBB score of 14.6 ± 2.6. Three rats that received only one injection bilaterally centered at L-2 (three animals) had a mean BBB score of 3.2 ± 2. Histological examination revealed variable loss of motor neurons limited to the injection site. There was no correlation between motor neuron loss and BBB score. Conclusions. Interneuron loss centered on the L-2 segment induces lasting paraplegia independent of motor neuron loss and white matter damage, supporting earlier suggestions that circuitry critical to the generator of locomotor activity (the central pattern generator) resides in this area. This injury model may prove ideal for studies of neuron replacement strategies.

Neonatal Death in Mice Lacking Cardiotrophin-like Cytokine is Associated with Multifocal Neuronal Hypoplasia

2008 ◽  
Vol 46 (3) ◽  
pp. 514-519 ◽  
Author(s):  
X. Zou ◽  
B. Bolon ◽  
J. K. Pretorius ◽  
C. Kurahara ◽  
J. McCabe ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Ventral Horn ◽  
Lumbar Spinal Cord ◽  
Facial Nucleus ◽  
In Ovo ◽  
Neuron Survival ◽  
Motor Neuron Survival ◽  
Lumbar Spinal

Mice with null mutations of ciliary neurotrophic factor (Cntf) receptor alpha (Cntf-Rα), or cytokine-like factor 1 (Clf), one component of Cntf-II (a heterodimeric Cntf-Rα ligand), die as neonates from motor neuron loss affecting the facial nucleus and ventral horn of the lumbar spinal cord. Exposure to cardiotrophin-like cytokine (Clc), the other putative Cntf-II element, supports motor neuron survival in vitro and in ovo. Confirmation that Clc ablation induces an equivalent phenotype to Clf deletion would support a role for Clc in the functional Cntf-II complex. In this study, Clc knockout mice had decreased facial motility, did not suckle, died within 24 hours, and had 32% and 29% fewer motor neurons in the facial nucleus and lumbar ventral horn, respectively; thus, Clc is essential for motor neuron survival during development. The concordance of the Clc knockout phenotype with those of mice lacking Cntf-Rα or Clf bolsters the hypothesis that Clc participates in Cntf-II.

scholarly journals Aggressive FUS-Mutant Motor Neuron Disease Without Profound Spinal Cord Pathology

2020 ◽  
Vol 79 (4) ◽  
pp. 365-369 ◽  
Author(s):  
Yan Chen Wongworawat ◽  
Yin Allison Liu ◽  
Ravi Raghavan ◽  
Charles L White ◽  
Robin Dietz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Cell Loss ◽  
Anterior Horn ◽  
Low Grade ◽  
Thoracic Spinal Cord ◽  
Cytoplasmic Inclusions ◽  
Thoracic Spinal

Abstract A 29-year-old man presented with rapidly progressive severe neck weakness, asymmetrical bilateral upper extremity weakness, bulbar dysfunction, profound muscle wasting, and weight loss. Within 1 year, his speech became unintelligible, he became gastrostomy- and tracheostomy/ventilator-dependent, and wheelchair bound. Electrophysiology suggested motor neuron disease. Whole exome sequencing revealed a heterozygous pathogenic variant in the fused in sarcoma gene (FUS), c.1574C&gt;T,p. R525L, consistent with autosomal dominant amyotrophic lateral sclerosis. Autopsy revealed extensive denervation atrophy of skeletal musculature. Surprisingly, there was only minimal patchy depletion of motor neurons within the cervico-thoracic spinal cord anterior horn cells, and the tracts were largely preserved. TDP-43 inclusions were absent. Abnormal expression of FUS mutation product (cytoplasmic inclusions) was demonstrated by immunohistochemistry within anterior horn motor neurons. The most prominent finding was a disparity between profound neck weakness and relatively low-grade anterior horn cell loss or tract degeneration in the cervico-thoracic cord.

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.

Lower Motor Neuron Disease with Accumulation of Neurofilaments in a Cat

1976 ◽  
Vol 13 (6) ◽  
pp. 428-435 ◽  
Author(s):  
M. Vandevelde ◽  
C. E. Greene ◽  
E. J. Hoff
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Histological Examination ◽  
Muscle Atrophy ◽  
Motor Neurons ◽  
Nerve Cells ◽  
Lower Motor Neuron ◽  
Motor Neuron Diseases ◽  
Lower Motor Neuron Disease

A young cat had signs of tetraparesis that progressed to tetraplegia within a few weeks. Clinically, there was lower motor neuron disease with areflexia and muscle atrophy in all limbs. Degeneration of the motor neurons in the spinal cord was seen on histological examination. Ultrastructurally, the degeneration of nerve cells was characterized by abnormal proliferation of neurofilaments. These findings were compared to other motor neuron diseases and neurofibrillary accumulations in man and animals.

scholarly journals Therapeutic Hypothermia Improves Hind Limb Motor Outcome and Attenuates Oxidative Stress and Neuronal Damage in the Lumbar Spinal Cord Following Cardiac Arrest

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 38
Author(s):  
Ji Hyeon Ahn ◽  
Tae-Kyeong Lee ◽  
Bora Kim ◽  
Jae-Chul Lee ◽  
Hyun-Jin Tae ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Therapeutic Hypothermia ◽  
Hind Limb ◽  
Neuronal Damage ◽  
Ventral Horn ◽  
Lumbar Spinal Cord ◽  
Neuronal Protection ◽  
Endogenous Antioxidants ◽  
Lumbar Spinal

Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in the anterior horn in the lumbar spinal cord in a rat model of asphyxial CA (ACA). A total of 77 adult male Sprague–Dawley rats were randomized into five groups: normal, sham ACA plus (+) normothermia, ACA + normothermia, sham ACA + hypothermia, and ACA + hypothermia. ACA was induced for 5 min by injecting vecuronium bromide. Therapeutic hypothermia was applied after return of spontaneous circulation (ROSC) via rapid cooling with isopropyl alcohol wipes, which was maintained at 33 ± 0.5 °C for 4 h. Normothermia groups were maintained at 37 ± 0.2 °C for 4 h. Neuronal protection, microgliosis, oxidative stress, and changes of endogenous antioxidants were evaluated at 12 h, 1 day, and 2 days after ROSC following ACA. ACA resulted in neuronal damage from 12 h after ROSC and evoked obvious degeneration/loss of spinal neurons in the ventral horn at 1 day after ACA, showing motor deficit of the hind limb. In addition, ACA resulted in a gradual increase in microgliosis with time after ACA. Therapeutic hypothermia significantly reduced neuronal loss and attenuated hind limb dysfunction, showing that hypothermia significantly attenuated microgliosis. Furthermore, hypothermia significantly suppressed ACA-induced increases of superoxide anion production and 8-hydroxyguanine expression, and significantly increased superoxide dismutase 1 (SOD1), SOD2, catalase, and glutathione peroxidase. Taken together, hypothermic therapy was found to have a substantial impact on changes in ACA-induced microglia activation, oxidative stress factors, and antioxidant enzymes in the ventral horn of the lumbar spinal cord, which closely correlate with neuronal protection and neurological performance after ACA.

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