Production of Dopamine by Aromatic l-Amino Acid Decarboxylase Cells after Spinal Cord Injury

2016 ◽  
Vol 33 (12) ◽  
pp. 1150-1160 ◽  
Author(s):  
Li-Qun Ren ◽  
Jacob Wienecke ◽  
Hans Hultborn ◽  
Mengliang Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Amino Acid ◽  
Acid Decarboxylase ◽  
Amino Acid Decarboxylase ◽  
Cord Injury

scholarly journals Spinal Cord Injury Enables Aromatic L-Amino Acid Decarboxylase Cells to Synthesize Monoamines

2014 ◽  
Vol 34 (36) ◽  
pp. 11984-12000 ◽  
Author(s):  
J. Wienecke ◽  
L.-Q. Ren ◽  
H. Hultborn ◽  
M. Chen ◽  
M. Moller ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Amino Acid ◽  
Acid Decarboxylase ◽  
Amino Acid Decarboxylase ◽  
Cord Injury

scholarly journals Synthesis, transport, and metabolism of serotonin formed from exogenously applied 5-HTP after spinal cord injury in rats

2014 ◽  
Vol 111 (1) ◽  
pp. 145-163 ◽  
Author(s):  
Yaqing Li ◽  
Lisa Li ◽  
Marilee J. Stephens ◽  
Dwight Zenner ◽  
Katherine C. Murray ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Brain Stem ◽  
Tryptophan Hydroxylase ◽  
Acid Decarboxylase ◽  
Amino Acid Decarboxylase ◽  
Cord Injury ◽  
Motoneuron Activity

Spinal cord transection leads to elimination of brain stem-derived monoamine fibers that normally synthesize most of the monoamines in the spinal cord, including serotonin (5-hydroxytryptamine, 5-HT) synthesized from tryptophan by enzymes tryptophan hydroxylase (TPH, synthesizing 5-hydroxytryptophan, 5-HTP) and aromatic l-amino acid decarboxylase (AADC, synthesizing 5-HT from 5-HTP). Here we examine whether spinal cord caudal to transection remains able to manufacture and metabolize 5-HT. Immunolabeling for AADC reveals that, while most AADC is confined to brain stem-derived monoamine fibers in spinal cords from normal rats, caudal to transection AADC is primarily found in blood vessel endothelial cells and pericytes as well as a novel group of neurons (NeuN positive and GFAP negative), all of which strongly upregulate AADC with injury. However, immunolabeling for 5-HT reveals that there is no detectable endogenous 5-HT synthesis in any structure in the spinal cord caudal to a chronic transection, including in AADC-containing vessels and neurons, consistent with a lack of TPH. In contrast, when we applied exogenous 5-HTP (in vitro or in vivo), AADC-containing vessels and neurons synthesized 5-HT, which contributed to increased motoneuron activity and muscle spasms (long-lasting reflexes, LLRs), by acting on 5-HT2receptors (SB206553 sensitive) located on motoneurons (TTX resistant). Blocking monoamine oxidase (MAO) markedly increased the sensitivity of the motoneurons (LLR) to 5-HTP, more than it increased the sensitivity of motoneurons to 5-HT, suggesting that 5-HT synthesized from AADC is largely metabolized in AADC-containing neurons and vessels. In summary, after spinal cord injury AADC is upregulated in vessels, pericytes, and neurons but does not endogenously produce 5-HT, whereas when exogenous 5-HTP is provided AADC does produce functional amounts of 5-HT, some of which is able to escape metabolism by MAO, diffuse out of these AADC-containing cells, and ultimately act on 5-HT receptors on motoneurons.

scholarly journals Spinal Cord Hemisection Facilitates Aromatic L-Amino Acid Decarboxylase Cells to Produce Serotonin in the Subchronic but Not the Chronic Phase

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Bushra Azam ◽  
Jacob Wienecke ◽  
Dennis Bo Jensen ◽  
Aleena Azam ◽  
Mengliang Zhang
Keyword(s):  
Spinal Cord ◽  
Amino Acid ◽  
Chronic Phase ◽  
Acid Decarboxylase ◽  
Partial Loss ◽  
Adult Rats ◽  
Amino Acid Decarboxylase ◽  
Thoracic Level ◽  
Plastic Changes ◽  
Spinal Cord Hemisection

Neuromodulators, such as serotonin (5-hydroxytryptamine, 5-HT) and noradrenalin, play an essential role in regulating the motor and sensory functions in the spinal cord. We have previously shown that in the rat spinal cord the activity of aromatic L-amino acid decarboxylase (AADC) cells to produce 5-HT from its precursor (5-hydroxytryptophan, 5-HTP) is dramatically increased following complete spinal cord transection. In this study, we investigated whether a partial loss of 5-HT innervation could similarly increase AADC activity. Adult rats with spinal cord hemisected at thoracic level (T11/T12) were used with a postoperation interval at 5 days or 60 days. Using immunohistochemistry, first, we observed a significant reduction in the density of 5-HT-immunoreactive fibers in the spinal cord below the lesion on the injured side for both groups. Second, we found that the AADC cells were similarly expressed on both injured and uninjured sides in both groups. Third, increased production of 5-HT in AADC cells following 5-HTP was seen in 5-day but not in 60-day postinjury group. These results suggest that plastic changes of the 5-HT system might happen primarily in the subchronic phase and for longer period its function could be compensated by plastic changes of other intrinsic and/or supraspinal modulation systems.

scholarly journals Exercise training modulates glutamic acid decarboxylase-65/67 expression through TrkB signaling to ameliorate neuropathic pain in rats with spinal cord injury

2020 ◽  
Vol 16 ◽  
pp. 174480692092451
Author(s):  
Xiangzhe Li ◽  
Qinghua Wang ◽  
Jie Ding ◽  
Sheng Wang ◽  
Chuanming Dong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Exercise Training ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Acid Decarboxylase ◽  
Cord Injury ◽  
Tropomyosin Related Kinase B ◽  
Glutamic Acid Decarboxylase 65

Neuropathic pain is one of the most frequently stated complications after spinal cord injury. In post-spinal cord injury, the decrease of gamma aminobutyric acid synthesis within the distal spinal cord is one of the main causes of neuropathic pain. The predominant research question of this study was whether exercise training may promote the expression of glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67, which are key enzymes of gamma aminobutyric acid synthesis, within the distal spinal cord through tropomyosin-related kinase B signaling, as its synthesis assists to relieve neuropathic pain after spinal cord injury. Animal experiment was conducted, and all rats were allocated into five groups: Sham group, SCI/PBS group, SCI-TT/PBS group, SCI/tropomyosin-related kinase B-IgG group, and SCI-TT/tropomyosin-related kinase B-IgG group, and then T10 contusion SCI model was performed as well as the tropomyosin-related kinase B-IgG was used to block the tropomyosin-related kinase B activation. Mechanical withdrawal thresholds and thermal withdrawal latencies were used for assessing pain-related behaviors. Western blot analysis was used to detect the expression of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-REB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. Immunohistochemistry was used to analyze the distribution of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord dorsal horn. The results showed that exercise training could significantly mitigate the mechanical allodynia and thermal hyperalgesia in post-spinal cord injury and increase the synthesis of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. After the tropomyosin-related kinase B signaling was blocked, the analgesic effect of exercise training was inhibited, and in the SCI-TT/tropomyosin-related kinase B-IgG group, the synthesis of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord were also significantly reduced compared with the SCI-TT/PBS group. This study shows that exercise training may increase the glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67 expression within the spinal cord dorsal horn through the tropomyosin-related kinase B signaling, and this mechanism may play a vital role in relieving the neuropathic pain of rats caused by incomplete SCI.

scholarly journals Peripherally Delivered Glutamic Acid Decarboxylase Gene Therapy for Spinal Cord Injury Pain

2004 ◽  
Vol 10 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Jun Liu ◽  
Darren Wolfe ◽  
Shuanglin Hao ◽  
Shaohua Huang ◽  
Joseph C. Glorioso ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Acid Decarboxylase ◽  
Cord Injury ◽  
Spinal Cord Injury Pain

Role of the blood-spinal cord barrier in posttraumatic syringomyelia

2009 ◽  
Vol 11 (6) ◽  
pp. 696-704 ◽  
Author(s):  
Sarah J. Hemley ◽  
B. Biotech ◽  
Jian Tu ◽  
Marcus A. Stoodley
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Amino Acid ◽  
Vascular Permeability ◽  
Neurological Deficits ◽  
Time Points ◽  
Functional Integrity ◽  
Cord Injury ◽  
Posttraumatic Syringomyelia ◽  
Blood Spinal Cord Barrier

Object Posttraumatic syringomyelia produces a significant burden of pain and neurological deficits in patients with spinal cord injury. The mechanism of syrinx formation is unknown and treatment is often ineffective. A possible explanation for syrinx formation is fluid leakage from the microcirculation in the presence of a compromised blood-spinal cord barrier (BSCB). The aim of this study was to investigate the structural and functional integrity of the BSCB in a model of posttraumatic syringomyelia. Methods The excitotoxic amino acid and arachnoiditis model of syringomyelia was used in 27 Sprague-Dawley rats. Structural integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen (EBA), and loss of functional integrity was assessed by extravasation of intravascular horseradish peroxidase. Animals were studied after 3 days, or at 1, 3, 6, or 12 weeks after surgery. There were laminectomy-only and saline injection control animals for comparison at each time point. Results Syrinxes formed in 16 of the 17 animals injected with excitotoxic amino acid. Loss of structural and functional integrity of the BSCB in syrinx animals was noted at all time points. Disruption of the BSCB was most dramatic in tissue adjacent to the syrinx, and in the central and dorsal gray matter. Changes in EBA expression generally corresponded with altered vascular permeability, although in the acute stages, widespread vascular permeability occurred without a corresponding decrease in EBA expression. At the later time points (3–12 weeks) EBA expression was often absent, although no vascular leakage was observed. Conclusions This study demonstrated a prolonged structural and functional disruption of the BSCB in this model of posttraumatic syringomyelia. Loss of functional integrity of the BSCB, with fluid entering the interstitial space of the spinal cord, may contribute to initial cyst formation after spinal cord injury and subsequent enlargement of the cyst, to produce posttraumatic syringomyelia.

scholarly journals Protective effects of glucosamine-kynurenic acid after compression-induced spinal cord injury in the rat

2012 ◽  
Vol 7 (6) ◽  
pp. 996-1004 ◽  
Author(s):  
Andrea Korimová ◽  
Dáša Cížková ◽  
Jozsef Toldi ◽  
László Vécsei ◽  
Ivo Vanický
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Amino Acid ◽  
Kynurenic Acid ◽  
Excitatory Amino Acid ◽  
Protective Effects ◽  
Tissue Destruction ◽  
Amino Acid Receptors ◽  
Cord Injury ◽  
Secondary Tissue

AbstractKynurenic acid (KYNA), a metabolite of the essential amino acid L-tryptophan, is a broad spectrum antagonist of excitatory amino acid receptors, which have also anticonvulsant and neuroprotective properties. After spinal cord injury (SCI), excitotoxicity is considered to play a significant role in the processes of secondary tissue destruction in both grey and white matter of the spinal cord. In this study, we have tested the potential therapeutic effect of glucosamine-kynurenic acid, administered after experimental compression-induced SCI in the rat. Spinal application of glucosamine-kynurenic acid continually for 24 hr after experimental SCI resulted in improved motor function recovery, beginning from the first week of evaluation and continuing until the end of the study (4 weeks). After 4 weeks’ survival, quantitative morphometric analysis of the spinal cord showed that glucosamine-kynurenic acid treatment was associated with improved tissue preservation at the lesion site. These findings indicate that spinal application of glucosaminekynurenic acid is neuroprotective and improves the outcome even when administered after spinal trauma. Our results suggest that the treatments initiated in early posttraumatic period can alleviate secondary injury and improve the final outcome after SCI.

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