scholarly journals ASIC3-dependent spinal cord nociceptive signaling in cutaneous pain induced by lysophosphatidyl-choline

2020 ◽  
Author(s):  
Ludivine Pidoux ◽  
Kevin Delanoe ◽  
Eric Lingueglia ◽  
Emmanuel Deval
Keyword(s):  
Spinal Cord ◽  
Neuron Activity ◽  
Dorsal Spinal Cord ◽  
Spinal Cord Neurons ◽  
Lysophosphatidyl Choline ◽  
Nociceptive Pathway ◽  
Nociceptive Fibers ◽  
Cord Neuron ◽  
Peripheral Sensory

ABSTRACTLysophosphatidyl-choline (LPC), a member of the phospholipid family, has recently emerged as an interesting new player in pain. It has been proposed to mediate pain through Acid-Sensing Ion Channel 3 (ASIC3), a pain-related channel mainly expressed in peripheral sensory neurons. LPC potentiates ASIC3 current evoked by mild acidifications, but can also activate the channel at physiological pH, and its local injection in rodents evokes ASIC3-dependent pain. We combine here in vivo recordings of spinal cord neuron activity with subcutaneous LPC injection to analyze the mechanism of action associated with the LPC-induced, ASIC3-dependent pain in peripheral and spinal cord neurons. We show that a single cutaneous injection of LPC exclusively affects the nociceptive pathway. It evokes an ASIC3-dependent short-term sensitization of nociceptive fibers that drives hyperexcitability of projecting neurons within the dorsal spinal cord without apparent central sensitization.

scholarly journals Regeneration of dorsal spinal cord neurons after injury via in situ NeuroD1-mediated astrocyte-to-neuron conversion

2019 ◽  
Author(s):  
Brendan Puls ◽  
Yan Ding ◽  
Fengyu Zhang ◽  
Mengjie Pan ◽  
Zhuofan Lei ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Cell Fate ◽  
High Efficiency ◽  
Reactive Astrocytes ◽  
Dorsal Spinal Cord ◽  
Spinal Cord Neurons ◽  
Cord Injury ◽  
Dorsal Spinal

AbstractSpinal cord injury (SCI) often leads to impaired motor and sensory functions, partially because the injury-induced neuronal loss cannot be easily replenished through endogenous mechanisms. In vivo neuronal reprogramming has emerged as a novel technology to regenerate neurons from endogenous glial cells by forced expression of neurogenic transcription factors. We have previously demonstrated successful astrocyte-to-neuron conversion in mouse brains with injury or Alzheimer’s disease by overexpressing a single neural transcription factor NeuroD1 via retroviruses. Here we demonstrate regeneration of dorsal spinal cord neurons from reactive astrocytes after SCI via adeno-associated virus (AAV), a more clinically relevant gene delivery system. We find that NeuroD1 converts reactive astrocytes into neurons in the dorsal horn of stab-injured spinal cord with high efficiency (∼95%). Interestingly, NeuroD1-converted neurons in the dorsal horn mostly acquire glutamatergic neuronal subtype, expressing spinal cord-specific markers such as Tlx3 but not brain-specific markers such as Tbr1, suggesting that the astrocytic lineage and local microenvironment affect the cell fate of conversion. Electrophysiological recordings show that the NeuroD1-converted neurons can functionally mature and integrate into local spinal cord circuitry by displaying repetitive action potentials and spontaneous synaptic responses. We further show that NeuroD1-mediated neuronal conversion can occur in the contusive SCI model, allowing future studies of evaluating this reprogramming technology for functional recovery after SCI. In conclusion, this study may suggest a paradigm shift for spinal cord repair using in vivo astrocyte-to-neuron conversion technology to generate functional neurons in the grey matter.

scholarly journals State-Dependent Changes in Glutamate, Glycine, GABA, and Dopamine Levels in Cat Lumbar Spinal Cord

2008 ◽  
Vol 100 (2) ◽  
pp. 598-608 ◽  
Author(s):  
N. Taepavarapruk ◽  
P. Taepavarapruk ◽  
J. John ◽  
Y. Y. Lai ◽  
J. M. Siegel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Rem Sleep ◽  
High Performance ◽  
Glycine Receptor ◽  
Lumbar Spinal Cord ◽  
Neuron Activity ◽  
Neural Pathways ◽  
Spinal Interneurons

Recent studies have indicated that the glycine receptor antagonist strychnine and the γ-aminobutyric acid type A (GABAA) receptor antagonist bicuculline reduced the rapid-eye-movement (REM) sleep-specific inhibition of sensory inflow via the dorsal spinocerebellar tract (DSCT). These findings imply that the spinal release of glycine and GABA may be due directly to the REM sleep-specific activation of reticulospinal neurons and/or glutamate-activated last-order spinal interneurons. This study used in vivo microdialysis and high-performance liquid chromatography analysis techniques to provide evidence for these possibilities. Microdialysis probes were stereotaxically positioned in the L3 spinal cord gray matter corresponding to sites where maximal cerebellar-evoked field potentials or individual DSCT and nearby spinoreticular tract (SRT) neurons could be recorded. Glutamate, glycine, and GABA levels significantly increased during REM sleep by approximately 48, 48, and 14%, respectively, compared with the control state of wakefulness. In contrast, dopamine levels significantly decreased by about 28% during REM sleep compared with wakefulness. During the state of wakefulness, electrical stimulation of the nucleus reticularis gigantocellularis (NRGc) at intensities sufficient to inhibit DSCT neuron activity, also significantly increased glutamate and glycine levels by about 69 and 45%, respectively, but not GABA or dopamine levels. We suggest that the reciprocal changes in the release of glutamate, glycine, and GABA versus dopamine during REM sleep contribute to the reduction of sensory inflow to higher brain centers via the DSCT and nearby SRT during this behavioral state. The neural pathways involved in this process likely include reticulo- and diencephalospinal and spinal interneurons.

scholarly journals In Vivo Neuronal Subtype-Specific Targets of Atoh1 (Math1) in Dorsal Spinal Cord

2011 ◽  
Vol 31 (30) ◽  
pp. 10859-10871 ◽  
Author(s):  
H. C. Lai ◽  
T. J. Klisch ◽  
R. Roberts ◽  
H. Y. Zoghbi ◽  
J. E. Johnson
Keyword(s):  
Spinal Cord ◽  
Dorsal Spinal Cord ◽  
Neuronal Subtype ◽  
Dorsal Spinal

Spinal cord neuron classes in embryos of the smooth newt Triturus vulgaris : a horseradish peroxidase and immunocytochemical study

1993 ◽  
Vol 340 (1291) ◽  
pp. 141-160 ◽  
Keyword(s):  
Spinal Cord ◽  
Horseradish Peroxidase ◽  
Ambystoma Mexicanum ◽  
Trunk Muscles ◽  
Longitudinal Distribution ◽  
Spinal Cord Neurons ◽  
Commissural Neurons ◽  
Smooth Newt ◽  
Triturus Vulgaris ◽  
Cord Neuron

Spinal cord neurons were investigated in embryos of Triturus vulgaris , the smooth newt, just prior to hatching. These embryos can swim if freed from their egg membranes. Horseradish peroxidase (HRP) labelling, together with GABA and glycine immunocytochemistry (ICC), revealed nine distinct anatomical classes of neuron. 1. Ventrolateral motorneurons with mainly dorsal dendrites, sometimes a descending central axon and peripheral axon innervating the trunk muscles. 2. Dorsal primary sensory Rohon-Beard neurons innervating skin and with dorsal ascending and descending axons in spinal cord. 3. Commissural interneurons with mid-cord unipolar soma, glycine-like immunoreactivity, dendrites on initial segment of ventral axon which crosses cord to ascend or branch. 4. Dorsolateral commissural interneurons with multipolar soma in dorsolateral position with dorsal dendrites and ventral axon which crosses and ascends or branches. 5. Giant dorsolateral commissural interneurons with large dorsolateral somata widely spaced (130- 250 µm spacing) with process projecting dorsally to other side, dorsolateral dendrites and ventral axon which crosses to ascend and branch. 6. Dorsolateral ascending interneurons in dorsolateral position with multipolar soma and ascending axon on same side. 7. Ascending interneurons with unipolar soma, GABA-like immunoreactivity and ascending axon on same side. 8. Descending interneurons with bi- or multi-polar soma, extensive dorsal and ventral dendrites, and descending axon on same side. They may also have ascending axons. 9. Kolmer-Agduhr cerebrospinal fluid contacting neurons with cilia and microvilli in lateral corners of neural canal, GABA-like immunoreactivity, no dendrites and ascending axon. Eight of the nine cell classes were found to bear a marked resemblance to neurons previously described in zebrafish and Xenopus embryos in terms of their anatomy, distribution and immunoreactivity to GABA and glycine. Homologies and possible functions are discussed. Giant dorsolateral commissural neurons, were not found in Xenopus or teleosts but were present in Ambystoma mexicanum and Neoceratodus . The regular, possibly segmental longitudinal distribution pattern of these cells within the cord is unusual amoung amphibian spinal neurons.

scholarly journals Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy

2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Changjiang Gu ◽  
Linwei Li ◽  
Yifan Huang ◽  
Dingfei Qian ◽  
Wei Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Reperfusion Injury ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Spinal Cord Ischemia ◽  
Neurological Dysfunction ◽  
Spinal Cord Neurons

Ischemia-reperfusion injury is the second most common injury of the spinal cord and has the risk of neurological dysfunction and paralysis, which can seriously affect patient quality of life. Salidroside (Sal) is an active ingredient extracted from Herba Cistanche with a variety of biological attributes such as antioxidant, antiapoptotic, and neuroprotective activities. Moreover, Sal has shown a protective effect in ischemia-reperfusion injury of the liver, heart, and brain, but its effect in ischemia-reperfusion injury of the spinal cord has not been elucidated. Here, we demonstrated for the first time that Sal pretreatment can significantly improve functional recovery in mice after spinal cord ischemia-reperfusion injury and significantly inhibit the apoptosis of neurons both in vivo and in vitro. Neurons have a high metabolic rate, and consequently, mitochondria, as the main energy-supplying suborganelles, become the main injury site of spinal cord ischemia-reperfusion injury. Mitochondrial pathway-dependent neuronal apoptosis is increasingly confirmed by researchers; therefore, Sal’s effect on mitochondria naturally attracted our attention. By means of a range of experiments both in vivo and in vitro, we found that Sal can reduce reactive oxygen species production through antioxidant stress to reduce mitochondrial permeability and mitochondrial damage, and it can also enhance the PINK1-Parkin signaling pathway and promote mitophagy to eliminate damaged mitochondria. In conclusion, our results show that Sal is beneficial to the protection of spinal cord neurons after ischemia-reperfusion injury, mainly by reducing apoptosis associated with the mitochondrial-dependent pathway, among which Sal’s antioxidant and autophagy-promoting properties play an important role.

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