DL -Homocysteic acid application disrupts calcium homeostasis and induces degeneration of spinal motor neurons in vivo

2002 ◽  
Vol 103 (5) ◽  
pp. 428-436 ◽  
Author(s):  
Róbert Adalbert ◽  
József Engelhardt ◽  
László Siklós
Keyword(s):  
Motor Neurons ◽  
Calcium Homeostasis ◽  
Homocysteic Acid ◽  
Spinal Motor Neurons ◽  
Spinal Motor

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 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 Real-time visualization of oxidative stress-mediated neurodegeneration of individual spinal motor neurons in vivo

Redox Biology ◽  
2018 ◽  
Vol 19 ◽  
pp. 226-234 ◽  
Author(s):  
Isabel Formella ◽  
Adam J. Svahn ◽  
Rowan A.W. Radford ◽  
Emily K. Don ◽  
Nicholas J. Cole ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Real Time ◽  
Motor Neurons ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Real Time Visualization

scholarly journals Optogenetic modulation of TDP-43 oligomerization fast-forwards ALS-related pathologies in the spinal motor neurons

2019 ◽  
Author(s):  
Kazuhide Asakawa ◽  
Hiroshi Handa ◽  
Koichi Kawakami
Keyword(s):  
Motor Neurons ◽  
Light Illumination ◽  
Short Term ◽  
Spinal Motor Neuron ◽  
Spinal Motor Neurons ◽  
Intrinsically Disordered ◽  
Spinal Motor ◽  
Lateral Sclerosis

AbstractCytoplasmic aggregation of TDP-43 characterizes degenerating neurons in most cases of amyotrophic lateral sclerosis (ALS), yet the mechanisms and cellular outcomes of TDP-43 pathology remain largely elusive. Here, we develop an optogenetic TDP-43 variant (opTDP-43), whose multimerization status can be modulated in vivo through external light illumination. Using the translucent zebrafish neuromuscular system, we demonstrate that short-term light stimulation reversibly induces cytoplasmic opTDP-43 mislocalization, but not aggregation, in the spinal motor neuron, leading to an axon outgrowth defect associated with myofiber denervation. In contrast, opTDP-43 forms pathological aggregates in the cytoplasm after longer-term illumination and seeds non-optogenetic TDP-43 aggregation. Furthermore, we find that an ALS-linked mutation in the intrinsically disordered region (IDR) exacerbates the light-dependent opTDP-43 toxicity on locomotor behavior. Together, our results propose that IDR-mediated TDP-43 oligomerization triggers both acute and long-term pathologies of motor neurons, which may be relevant to the pathogenesis and progression of ALS.

scholarly journals V3 Interneurons Regulate Locomotor Vigor by Recruitment of Spinal Motor Neurons During Fictive Swimming in Larval Zebrafish

2021 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Jacob E. Montgomery ◽  
Amanda J. Brunick ◽  
Jack H. Peck ◽  
Mark A. Masino
Keyword(s):  
Motor Control ◽  
Motor Neurons ◽  
Neuronal Population ◽  
Fine Motor ◽  
Spinal Interneurons ◽  
Spinal Motor Neurons ◽  
Larval Zebrafish ◽  
Spinal Motor ◽  
Spinal Network

ABSTRACTSurvival for vertebrate animals is dependent on the ability to successfully find food, locate a mate, and avoid predation. Each of these behaviors requires fine motor control, which is set by a combination of kinematic properties. For example, the frequency and amplitude (vigor; strength) of motor output combine to determine features of locomotion such as distance traveled and speed. Although there is a good understanding of how different populations of excitatory spinal interneurons establish locomotor frequency, there is not a mechanistic understanding for how locomotor vigor is established. Recent evidence indicates that locomotor vigor is regulated in part by subsets of identified excitatory spinal interneurons (INs), such as the V2a neuronal population in adult zebrafish. Here we provide evidence that the majority of V3 interneurons (V3-INs), which are a developmentally and genetically defined population of ventromedial glutamatergic spinal neurons, are active during fictive swimming. Further, that targeted ablation of V3-INs reduces the proportion of active MNs during fictive swimming, but ablation does not affect the locomotor frequencies produced. These data are consistent with a role of V3-INs in providing excitatory drive to spinal motor neurons during swimming in larval zebrafish, which suggests that locomotor vigor (but not locomotor frequency) may be regulated, in part, by V3-INs.SIGNIFICANCE STATEMENTCurrently, there is a fundamental lack of knowledge about the cellular and spinal network properties that produce locomotor vigor in vertebrates. Here we show, directly for the first time, that V3 interneurons in zebrafish larvae are active duringin vivofictive locomotion, and that targeted ablation of the spinal V3 interneuron population reduces the probability of motoneuron firing during fictive swimming. In contrast to V2a interneurons, ablation of V3 interneurons does not affect locomotor frequency, the fictive neural correlate of speed, which clarifies their role in motor control rather than rhythm generation. Thus, we propose that the V3 interneuron subpopulation is a source of excitation in the vertebrate locomotor neural circuitry that regulates locomotor vigor independently of speed.

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