Glutaminase Immunoreactivity and Enzyme Activity Is Increased in the Rat Dorsal Root Ganglion Following Peripheral Inflammation

Miller, Kenneth E.; Balbás, John C.; Benton, Richard; Lam, Travis; Edwards, Kristin M.; Kriebel, Richard M.; Schechter, Ruben

doi:10.1155/2012/414697

Cited by 21 publications

(46 citation statements)

References 51 publications

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“…The antisera used for GLS, VGLUT1, and VGLUT2 have been employed previously in our laboratory for rat DRG neurons (Miller et al, 2012, Crosby H., 2015, Bolt, 2016, Hoffman et al, 2016) and pre-absorption control studies in ICG and other rat tissues (colon, skin, cornea, sciatic nerve, DRG, TG, spinal cord) support the specificity of the three antibodies. Furthermore, quantitative image analysis allowed us to categorize immunoreactive neurons into moderate and high classes and exclude neurons that were non-immunoreactive.…”

Section: Discussionmentioning

confidence: 75%

“…GLS-ir was present in many rat ICG neurons as puncta found throughout the cytoplasm (Figure 1A,C; Hoffman et al, 2010; Miller et al, 2012; Crosby et al, 2015; Hoffman et al, 2016). Among 1318 ICG neurons analyzed (n=5 rats), the cell soma area ranged from 53.0 to 867.9µm 2 (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

“…In primary sensory neurons in DRG, neurotransmitter glutamate production utilizing the glutamate-glutamine cycle is important for sensory function (Miller et al, 1993, Miller et al, 2002, Miller et al, 2012). Phosphate-activated GLS, regulated by calcium (Ca 2+ ) and inorganic phosphate (P i ), is the synthetic enzyme for conversion of glutamine into glutamate for use as a neurotransmitter (Erecinska et al, 1990, Miller et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall

Wang

Miller

2016

Neuroscience

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The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system.

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Section: Discussionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall

Wang

Miller

2016

Neuroscience

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“…Glutamic acid (Glu) in vivo is produced from glutamine deamination (Erickson and Cerione 2010;List et al 2012;Marquez et al 2013). Glu is the most important excitatory amino acid in the excitatory neurotransmitter system, which plays a key role in learning, memory and central pain sensory conduction (de la Rosa et al 2009;Marquez et al 2006;Miller et al 2012). Previous studies have revealed that Glu is one of the most important neurotransmitters to mediate pain information transfer (Odai et al 2001;Toth et al 1992;Kazemi and Hoop 1991).…”

Section: Discussionmentioning

confidence: 99%

Glutaminase 1 is a potential biomarker for chronic post-surgical pain in the rat dorsal spinal cord using differential proteomics

et al. 2015

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Chronic post-surgical pain (CPSP) is a normal and significant symptom in clinical surgery, such as breast operation, biliary tract operation, cesarean operation, uterectomy and thoracic operation. Severe chronic post-surgical pain could increase post-surgical complications, including myocardial ischemia, respiratory insufficiency, pneumonia and thromboembolism. However, the underlying mechanism is still unknown. Herein, a rat CPSP model was produced via thoracotomy. After surgery, in an initial study, 5 out of 12 rats after surgery showed a significant decrease in mechanical withdrawal threshold and/or increase in the number of acetone-evoked responses, and therefore classified as the CPSP group. The remaining seven animals were classified as non-CPSP. Subsequently, open-chest operation was performed on another 30 rats and divided into CPSP and non-CPSP groups after 21-day observation. Protein expression levels in the dorsal spinal cord tissue were determined by 12.5 % SDS-PAGE. Finally, differently expressed proteins were identified by LC MS/MS and analyzed by MASCOT software, followed by Gene Ontology cluster analysis using PANTHER software. Compared with the non-CPSP group, 24 proteins were only expressed in the CPSP group and another 23 proteins expressed differentially between CPSP and non-CPSP group. Western blot further confirmed that the expression of glutaminase 1 (GLS1) was significantly higher in the CPSP than in the non-CPSP group. This study provided a new strategy to identify the spinal proteins, which may contribute to the development of chronic pain using differential proteomics, and suggested that GLS1 may serve as a potential biomarker for CPSP.

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“…Accordingly, exogenously administered glutamate activates peripheral glutamate receptors, resulting in depolarization of primary afferent C fibers and induction of pain-related behavior (Carlton et al, 1995; Jackson et al, 1995; deGroot et al, 2000; Tian et al, 2005). Interestingly, glutaminase, the enzyme catalyzing the synthesis of glutamate from the precursor glutamine, is up-regulated in rat DRG neurons during hindpaw inflammation (Hoffman and Miller, 2010; Miller et al, 2012). Therefore, it seemed plausible that tissue inflammation could drive changes in the transcript expression of VGLUTs.…”

Section: Discussionmentioning

confidence: 99%

Transcript expression of vesicular glutamate transporters in lumbar dorsal root ganglia and the spinal cord of mice – Effects of peripheral axotomy or hindpaw inflammation

et al. 2013

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Using specific riboprobes, we characterized the expression of VGLUT1-VGLUT3 transcripts in lumbar 4-5 (L4-5) DRGs and the thoracolumbar to lumbosacral spinal cord in male BALB/C mice after a 1- or 3-day hindpaw inflammation, or a 7-day sciatic nerve axotomy. Sham animals were also included. In sham and contralateral L4-5 DRGs of injured mice, VGLUT1-, VGLUT2- and VGLUT3 mRNAs were expressed in ~45%, ~69% or ~17% of neuron profiles (NPs), respectively. VGLUT1 was expressed in large and medium-sized NPs, VGLUT2 in NPs of all sizes, and VGLUT3 in small and medium-sized NPs. In the spinal cord, VGLUT1 was restricted to a number of NPs at thoracolumbar and lumbar segments, in what appears to be the dorsal nucleus of Clarke, and in mid laminae III-IV. In contrast, VGLUT2 was present in numerous NPs at all analyzed spinal segments, except the lateral aspects of the ventral horns, especially at the lumbar enlargement, where it was virtually absent. VGLUT3 was detected in a discrete number of NPs in laminae III-IV of the dorsal horn. Axotomy resulted in a moderate decrease in the number of DRG NPs expressing VGLUT3, whereas VGLUT1 and VGLUT2 were unaffected. Likewise, the percentage of NPs expressing VGLUT transcripts remained unaltered after hindpaw inflammation, both in DRGs and the spinal cord. Altogether, these results confirm previous descriptions on VGLUTs expression in adult mice DRGs, with the exception of VGLUT1, whose protein expression was detected in a lower percentage of mouse DRG NPs. A detailed account on the location of neurons expressing VGLUTs transcripts in the adult mouse spinal cord is also presented. Finally, the lack of change in the number of neurons expressing VGLUT1 and VGLUT2 transcripts after axotomy, as compared to data on protein expression, suggests translational rather than transcriptional regulation of VGLUTs after injury.

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Glutaminase Immunoreactivity and Enzyme Activity Is Increased in the Rat Dorsal Root Ganglion Following Peripheral Inflammation

Cited by 21 publications

References 51 publications

Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall

Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall

Glutaminase 1 is a potential biomarker for chronic post-surgical pain in the rat dorsal spinal cord using differential proteomics

Transcript expression of vesicular glutamate transporters in lumbar dorsal root ganglia and the spinal cord of mice – Effects of peripheral axotomy or hindpaw inflammation

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