scholarly journals The manipulation of spinal motor neuron axonal growth promotes spinal cord repair

2021 ◽  
Author(s):  
Feng Wang ◽  
Xinya Fu ◽  
Meiemei Li ◽  
Xingran Wang ◽  
Jile Xie ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Axonal Regeneration ◽  
Axonal Growth ◽  
Treatment Method ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Cord Injury ◽  
Spinal Cord Repair

The loss of motor function in patients with spinal cord injury (SCI) is primarily due to the severing of the corticospinal tract (CST). Spinal motor neurons are located in the anterior horn of the spinal cord, and as the lower neurons of the CST, they control voluntary movement. Furthermore, its intrinsic axonal growth ability is significantly stronger than that of cerebral cortex pyramid neurons, which are the upper CST neurons. Therefore, we established an axonal regeneration model of spinal motor neurons to investigate the feasibility of repairing SCI by promoting axonal regeneration of spinal motor neurons. We demonstrated that conditionally knocking out pten in mature spinal motor neurons drastically enhanced axonal regeneration in vivo, and the regenerating axons of the spinal motor neurons re-established synapses with other cells in the damaged spinal cord. Thus, this strategy may serve as a novel and effective treatment method for SCI.

scholarly journals Illuminating ALS Motor Neurons With Optogenetics in Zebrafish

2021 ◽  
Vol 9 ◽  
Author(s):  
Kazuhide Asakawa ◽  
Hiroshi Handa ◽  
Koichi Kawakami
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Rna Binding ◽  
The Body ◽  
Optical Methods ◽  
Light Illumination ◽  
Whole Cells ◽  
Spinal Motor Neurons ◽  
Spinal Motor

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Spinal motor neurons align along the spinal cord length within the vertebral column, and extend long axons to connect with skeletal muscles covering the body surface. Due to this anatomy, spinal motor neurons are among the most difficult cells to observe in vivo. Larval zebrafish have transparent bodies that allow non-invasive visualization of whole cells of single spinal motor neurons, from somas to the neuromuscular synapses. This unique feature, combined with its amenability to genome editing, pharmacology, and optogenetics, enables functional analyses of ALS-associated proteins in the spinal motor neurons in vivo with subcellular resolution. Here, we review the zebrafish skeletal neuromuscular system and the optical methods used to study it. We then introduce a recently developed optogenetic zebrafish ALS model that uses light illumination to control oligomerization, phase transition and aggregation of the ALS-associated DNA/RNA-binding protein called TDP-43. Finally, we will discuss how this disease-in-a-fish ALS model can help solve key questions about ALS pathogenesis and lead to new ALS therapeutics.

scholarly journals Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Youngjae Ryu ◽  
Toru Ogata ◽  
Motoshi Nagao ◽  
Yasuhiro Sawada ◽  
Ryohei Nishimura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Treatment Strategy ◽  
Spinal Reflex ◽  
Preemptive Treatment ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Cord Injury ◽  
Swimming Test

AbstractIn the majority of spinal cord injury (SCI) patients, spasticity develops in the subacute phase and chronically persists with muscle hypertonia. Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5-HT denervation is considered one of crucial factors for hyperexcitability of the spinal circuit. As a 5-HT signal modulator, selective serotonin re-uptake inhibitors (SSRIs) are ordinarily prescribed for diseases associated with 5-HT in the CNS, and are known for their ability to increase 5-HT levels as well as to desensitize 5-HTR. Here, we hypothesized that early SSRI administration as a preemptive treatment strategy would effectively prevent the onset of spasticity. We used a rat model of contusive SCI and administered escitalopram during the first 4 weeks after injury, which is the period required for spasticity development in rodent models. We performed a swimming test to quantify spastic behaviors and conducted the Hoffman reflex test as well as histological analyses for 5-HT2AR and KCC2 expressions. Four weeks of escitalopram administration suppressed spastic behaviors during the swimming test and reduced the population of spasticity-strong rats. Moreover, the treatment resulted in decreased immunoreactivity of 5-HT2AR in the spinal motor neurons. Result of the H-reflex test and membrane expression of KCC2 were not significantly altered. In summary, early escitalopram administration could prevent the onset of spastic behaviors via regulation of 5-HT system after SCI, but could not modulate exaggerated spinal reflex. Our results suggest a novel application of SSRIs for preventative treatment of spasticity.

scholarly journals Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michael D. Sunshine ◽  
Antonino M. Cassarà ◽  
Esra Neufeld ◽  
Nir Grossman ◽  
Thomas H. Mareci ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Drug Overdose ◽  
Cervical Spinal Cord ◽  
Opioid Overdose ◽  
Electrode Position ◽  
Spinal Motor Neurons ◽  
Cord Injury ◽  
Low Amplitude

AbstractRespiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.

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