Orexin-A potentiates glycine currents by activating OX1R and IP3/Ca2+/PKC signaling pathways in spinal cord ventral horn neurons

2021 ◽  
Vol 169 ◽  
pp. 196-204
Author(s):  
Na Jin ◽  
Su-Yue Zhu ◽  
Xin-Yu Yang ◽  
Cheng Zhen ◽  
Yan Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathways ◽  
Ventral Horn ◽  
Orexin A ◽  
Pkc Signaling

Distribution of substance P in the spinal cord of patients with syringomyelia

1996 ◽  
Vol 84 (6) ◽  
pp. 992-998 ◽  
Author(s):  
Thomas H. Milhorat ◽  
Harrison T. M. Mu ◽  
Carole C. LaMotte ◽  
Ade T. Milhorat
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Dorsal Horn ◽  
Ventral Horn ◽  
Immunohistochemical Method ◽  
Positive Staining ◽  
Content Type ◽  
Normal Individuals ◽  
Neurologically Normal ◽  
Intermediolateral Nucleus

✓ The distribution of substance P, a putative neurotransmitter and pain-related peptide, was studied using the peroxidase—antiperoxidase immunohistochemical method in the spinal cords obtained from autopsy of 10 patients with syringomyelia and 10 age- and sex-matched, neurologically normal individuals. Substance P immunoreactivity was present in axons and in terminal-like processes in close apposition to neurons in the first, second, and third laminae of the dorsal horn. Smaller amounts of peroxidase-positive staining were found in the fifth lamina of the dorsal horn, the intermediolateral nucleus, the intermediomedial nucleus, and the ventral horn. In nine of 10 patients with syringomyelia, there was a substantial increase in substance P immunoreactivity in the first, second, third, and fifth laminae below the level of the lesion. A marked reduction or absence of staining was present in segments of the spinal cord occupied by the syrinx. Central cavities produced bilateral abnormalities, whereas eccentric cavities produced changes that were ipsilateral to the lesion. No alterations in staining were found in the spinal cord of an asymptomatic patient with a small central syrinx. The authors conclude that syringomyelia can be associated with abnormalities in spinal cord levels of substance P, which may affect the modulation and perception of pain.

scholarly journals Modulation of spinal motor networks by astrocyte-derived adenosine is dependent on D1-like dopamine receptor signaling

2018 ◽  
Vol 120 (3) ◽  
pp. 998-1009 ◽  
Author(s):  
David Acton ◽  
Matthew J. Broadhead ◽  
Gareth B. Miles
Keyword(s):  
Spinal Cord ◽  
Protein Kinase ◽  
Dopamine Receptor ◽  
Kinase Inhibitor ◽  
Ventral Horn ◽  
Skf 38393 ◽  
Network Activity ◽  
Related Activity ◽  
Burst Frequency ◽  
Spinal Motor

Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behavior. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysis of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signaling pathway; however, adenosine also modulates ventral horn circuits by dopamine-independent pathways. Here, we demonstrate that adenosine produced upon astrocytic stimulation modulates locomotor-related activity by counteracting the excitatory effects of D1LR signaling and does not act by previously described dopamine-independent pathways. In spinal cord preparations from postnatal mice, a D1LR agonist, SKF 38393, increased the frequency of locomotor-related bursting induced by 5-hydroxytryptamine and N-methyl-d-aspartate. Bath-applied adenosine reduced burst frequency only in the presence of SKF 38393, as did adenosine produced after activation of protease-activated receptor-1 to stimulate astrocytes. Furthermore, the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine enhanced burst frequency only in the presence of SKF 38393, indicating that endogenous adenosine produced by astrocytes during network activity also acts by modulating D1LR signaling. Finally, modulation of bursting by adenosine released upon stimulation of astrocytes was blocked by protein kinase inhibitor-(14–22) amide, a protein kinase A (PKA) inhibitor, consistent with A1R-mediated antagonism of the D1LR/adenylyl cyclase/PKA pathway. Together, these findings support a novel, astrocytic mechanism of metamodulation within the mammalian spinal cord, highlighting the complexity of the molecular interactions that specify motor output. NEW & NOTEWORTHY Astrocytes within the spinal cord produce adenosine during ongoing locomotor-related activity or when experimentally stimulated. Here, we show that adenosine derived from astrocytes acts at A1 receptors to inhibit a pathway by which D1-like receptors enhance the frequency of locomotor-related bursting. These data support a novel form of metamodulation within the mammalian spinal cord, enhancing our understanding of neuron-astrocyte interactions and their importance in shaping network activity.

A new dopaminergic terminal plexus in the ventral horn of rat spinal cord

1989 ◽  
Vol 9 ◽  
pp. 141
Author(s):  
Muneyasu Shirouzu ◽  
Takehiko Anraku ◽  
Yoshifumi Iwashita ◽  
Masami Yoshida
Keyword(s):  
Spinal Cord ◽  
Ventral Horn ◽  
Rat Spinal Cord ◽  
Dopaminergic Terminal

Transient decrease of acetylcholinesterase in ventral horn neurons caudal to a low thoracic spinal cord hemisection in the adult rat

1996 ◽  
Vol 714 (1-2) ◽  
pp. 177-184 ◽  
Author(s):  
Wilhelm Nacimiento ◽  
Bernd Schlözer ◽  
Gary A. Brook ◽  
Lajos Tóth ◽  
Rudolf Töpper ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Ventral Horn ◽  
Thoracic Spinal Cord ◽  
Adult Rat ◽  
Transient Decrease ◽  
Thoracic Spinal ◽  
Spinal Cord Hemisection

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.

Impaired Ca 2+ handling in resistance arteries from genetically obese Zucker rats: Role of the PI3K, ERK1/2 and PKC signaling pathways

2018 ◽  
Vol 152 ◽  
pp. 114-128 ◽  
Author(s):  
Ana Sánchez ◽  
Cristina Contreras ◽  
Belén Climent ◽  
Alejandro Gutiérrez ◽  
Mercedes Muñoz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Zucker Rats ◽  
Resistance Arteries ◽  
Pkc Signaling ◽  
Obese Zucker Rats

Corydalis Saxicola Bunting Total Alkaloids Inhibits Paclitaxel-Induced Peripheral Neuropathy By Regulating PKCε-TRPV1 and p38 MAPK-TRPV1 Signaling Pathways

2021 ◽  
Author(s):  
chu xue ◽  
Si-Xue Liu ◽  
Jie Hu ◽  
Jin Huang ◽  
Hong-Min Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Peripheral Neuropathy ◽  
Protein Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Cell Model ◽  
Mrna Levels ◽  
Drg Neurons ◽  
Total Alkaloids ◽  
Tnf Α

Abstract Background: Corydalis saxicola Bunting, a traditional Chinese medicine, has been proven to work well in anti-inflammation, blood circulation improvement, hemostasis, analgesia. This study was designed to observe the effects and potential mechanism of Corydalis saxicola Bunting total alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN). Materials and methods: Following 4 times intraperitoneal injections of paclitaxel (2 mg/kg) and intragastrically (i.g.) administrated at 30 or 120 mg/kg CSBTA, mechanical and thermal allodynia and hyperalgesia in rats were tested. After 40 days, serum was collected for the detection of PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and protein and gene expression of CGRP, SP, TRPV1, p38, and PKCε were analyzed by Western-blot or RT-qPCR. Parallelly, the PIPN cell model was also established in primary DRG neurons by paclitaxel stimulation (300 nM, 5 d). We examined PGE2, TNF-α and CGRP mRNA levels, and the protein expression on the PKCε-TRPV1 and p38 MAPK-TRPV1 pathways in PIPN cell model with or without CSBTA (25 μg/ml and 50 μg/ml). Results: The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia in PIPN rats, regulated the contents of cytokines and neuropeptides in different tissues and cell models. CSBTA significantly decreased the protein expression of PKCε-TRPV1 and p38 MAPK-TRPV1 signaling pathways in the spinal cord and DRG tissues in the PIPN animal model and primary DRG neurons. Conclusion: Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy.

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