Birthdate study of GABAergic neurons in the lumbar spinal cord of the glutamic acid decarboxylase 67-green fluorescent protein knock-in mouse

Background Findings to date indicate that nitrous oxide exerts its antinociceptive effect by activating descending noradrenergic neurons. The mechanism whereby descending inhibitory neurons, including noradrenergic neurons, produce antinociceptive effect remains unclear. Using c-Fos protein as a marker for neuronal activation, we examined whether spinal cord neurons activated by nitrous oxide are y-aminobutyric acid-mediated (GABAergic) neurons. Methods Adult male Fischer (a strain in which nitrous oxide shows strong antinociceptive properties) and Lewis (a strain in which nitrous oxide lacks antinociceptive properties) rats were exposed to either air (control) or nitrous oxide. Frozen sections of the spinal cord were either stained for c-Fos or double-stained for c-Fos and glutamic acid decarboxylase (a rate-limiting enzyme for GABA synthesis) and analyzed by standard or confocal microscopy. Results In Fischer rats, 90 min of 75% N2O administration increased the number of c-Fos-positive cells in the spinal cord approximately threefold as compared with the control group. The c-Fos-positive cells induced by nitrous oxide were almost entirely colocalized with glutamic acid decarboxylase-positive cells. In contrast, exposure did not change the number of c-Fos-positive cells in the spinal cord in Lewis rats. Conclusions Exposure to nitrous oxide activates GABAergic neurons in the spinal cord. The dose-dependence of GABAergic neuronal activation in the Fischer rats and its absence in the Lewis rat correlate with antinociceptive responses previously reported in these same circumstances. Together, we interpret these data to indicate that activation of GABAergic neurons in the spinal cord are involved in the antinociceptive action of nitrous oxide.

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

Molecular Pain ◽

10.1177/1744806920924511 ◽

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.

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Organization of GABA-Containing Neurons in Some Extrapyramidal Nuclei

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100023283 ◽

1980 ◽

Vol 7 (3) ◽

pp. 251-252 ◽

Cited By ~ 3

Author(s):

H.C. Fibiger

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Glutamic Acid ◽

Glutamic Acid Decarboxylase ◽

Current Knowledge ◽

Gabaergic Neurons ◽

Acid Decarboxylase ◽

Extrapyramidal System ◽

The Central Nervous System ◽

The Subject

SUMMARY:Nuclei of the extrapyramidal system contain among the highest levels of GABA and its synthesizing enzyme glutamic acid decarboxylase (GA D) in the central nervous system. In recent years the anatomical organization of GABAergic neurons in the extrapyramidal system has been the subject of considerable experimental enquiry. In this note, current knowledge concerning the origin and projections of GABAergic neurons in certain extrapyramidal nuclei is briefly reviewed.

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