scholarly journals Neuron Type-Specific Translatomes in Spinal Cords of Naïve and Neuropathic Mice

2020 ◽  
Author(s):  
R.R. Das Gupta ◽  
L. Scheurer ◽  
P. Pelczar ◽  
W.T. Ralvenius ◽  
H. Wildner ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Functional Organization ◽  
Affinity Purification ◽  
Expression Patterns ◽  
Inhibitory Neurons ◽  
Peripheral Nerve Damage ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Sensory Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, the molecular identity of the underlying neurons and signaling mechanisms are still only partially understood. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (VGLUT2+) and inhibitory GABA and/or glycinergic (VGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are primarily set apart by the expression of genes encoding transcription factors or genes related to the production, release or re-uptake of their principal neurotransmitters (glutamate, GABA or glycine). Subsequent gene ontology (GO) term analyses revealed that neuropeptide signaling-related GO terms were highly enriched in the excitatory population. Eleven neuropeptide genes displayed largely non-overlapping expression patterns closely adhering to the laminar and hence also functional organization of the spinal cord grey matter, suggesting that they may serve as major determinants of modality-specific processing. Since this modality-specific processing of sensory input is severely compromised in chronic, especially neuropathic, pain, we also investigated whether peripheral nerve damage changes the neuron typespecific translatome. In summary, our results suggest that neuropeptides contribute to modalityspecific sensory processing in the spinal cord but also indicate that altered sensory encoding in neuropathic pain states occurs independent of major translatome changes in the spinal neurons.

scholarly journals Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebecca Rani Das Gupta ◽  
Louis Scheurer ◽  
Pawel Pelczar ◽  
Hendrik Wildner ◽  
Hanns Ulrich Zeilhofer
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Functional Organization ◽  
Affinity Purification ◽  
Expression Patterns ◽  
Inhibitory Neurons ◽  
Dorsal Horn Neurons ◽  
Expression Of Genes ◽  
Excitatory Neurons ◽  
Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

scholarly journals Age- and sex-related ABC transporter expression in pyrethroid-susceptible and –resistant Aedes aegypti

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leslie C. Rault ◽  
Ellis J. Johnson ◽  
Scott T. O’Neal ◽  
Rui Chen ◽  
Sarah E. McComic ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Expression Patterns ◽  
Point Mutations ◽  
Resistance Mechanisms ◽  
Detoxification Enzymes ◽  
Insecticide Exposure ◽  
Expression Of Genes ◽  
Genes Encoding

AbstractResistance mechanisms to synthetic insecticides often include point mutations and increased expression of genes encoding detoxification enzymes. Since pyrethroids are the main adulticides used against Aedes aegypti, which vectors pathogens such as Zika virus, understanding resistance to this insecticide class is of significant relevance. We focused on adenosine triphosphate (ATP)-binding cassette (ABC) transporters in the pyrethroid-resistant Puerto Rico (PR) strain of Ae. aegypti. We investigated the expression patterns of six ABC transporters previously characterized as differentially expressed in insecticide-challenged mosquitoes, or increased mRNA expression in pyrethroid-resistant Ae. aegypti, by comparing PR to the Rockefeller (Rock) susceptible strain. No constitutive differential expression between strains was detected, but expression differences for these genes was influenced by sex and age, suggesting that their role is independent from resistance in PR. Instead, ABC transporters may be induced after insecticide exposure. Challenging mosquitoes with deltamethrin, with or without ABC transporter modulators, showed that Rock and PR responded differently, but a contribution of ABC transporters to deltamethrin toxicity is suspected. Moreover, the effect of dexamethasone, which enhanced the inhibition of nerve firing by deltamethrin, was observed using a Drosophila central nervous system preparation, showing synergy of these two compounds through the potential inhibition of ABC transporters.

scholarly journals Global Transcriptional Response of Bacillus subtilis to Treatment with Subinhibitory Concentrations of Antibiotics That Inhibit Protein Synthesis

2005 ◽  
Vol 49 (5) ◽  
pp. 1915-1926 ◽  
Author(s):  
Janine T. Lin ◽  
Mariah Bindel Connelly ◽  
Chris Amolo ◽  
Suzie Otani ◽  
Debbie S. Yaver
Keyword(s):  
Protein Synthesis ◽  
Bacillus Subtilis ◽  
Time Course ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Global Gene Expression ◽  
Protein Synthesis Inhibitors ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Subinhibitory Concentrations

ABSTRACT Global gene expression patterns of Bacillus subtilis in response to subinhibitory concentrations of protein synthesis inhibitors (chloramphenicol, erythromycin, and gentamicin) were studied by DNA microarray analysis. B. subtilis cultures were treated with subinhibitory concentrations of protein synthesis inhibitors for 5, 15, 30, and 60 min, and transcriptional patterns were measured throughout the time course. Three major classes of genes were affected by the protein synthesis inhibitors: genes encoding transport/binding proteins, genes involved in protein synthesis, and genes involved in the metabolism of carbohydrates and related molecules. Similar expression patterns for a few classes of genes were observed due to treatment with chloramphenicol (0.4× MIC) or erythromycin (0.5× MIC), whereas expression patterns of gentamicin-treated cells were distinct. Expression of genes involved in metabolism of amino acids was altered by treatment with chloramphenicol and erythromycin but not by treatment with gentamicin. Heat shock genes were induced by gentamicin but repressed by chloramphenicol. Other genes induced by the protein synthesis inhibitors included the yheIH operon encoding ABC transporter-like proteins, with similarity to multidrug efflux proteins, and the ysbAB operon encoding homologs of LrgAB that function to inhibit cell wall cleavage (murein hydrolase activity) and convey penicillin tolerance in Staphylococcus aureus.

scholarly journals Glutamate transporter dysfunction associated with nerve injury-induced pain in mice

2012 ◽  
Vol 107 (2) ◽  
pp. 649-657 ◽  
Author(s):  
Ian A. Napier ◽  
Sarasa A. Mohammadi ◽  
MacDonald J. Christie
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Excitatory Amino Acid ◽  
Expression Patterns ◽  
Glutamate Transporter ◽  
Synaptic Activity ◽  
Amino Acid Transporters ◽  
Functional Changes

Dysfunction at glutamatergic synapses has been proposed as a mechanism in the development of neuropathic pain. Here we sought to determine whether peripheral nerve injury-induced neuropathic pain results in functional changes to primary afferent synapses. Signs of neuropathic pain as well as an induction of glial fibrillary acidic protein in immunostained spinal cord sections 4 days after partial ligation of the sciatic nerve indicated the induction of neuropathic pain. We found that following nerve injury, no discernable change to kinetics of dl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) or N-methyl-d-aspartate receptor (NMDAR)-mediated evoked excitatory postsynaptic currents (eEPSCs) could be observed in dorsal horn (lamina I/II) neurons compared with those of naïve mice. However, we did find that nerve injury was accompanied by slowed decay of the early phase of eEPSCs in the presence of glutamate transporter inhibition by the competitive nontransportable inhibitor dl-threo-β-benzyloxyaspartic acid (TBOA). Concomitantly, expression patterns for the two major glutamate transporters in the spinal cord, excitatory amino acid transporters (EAAT) 1 and EAAT2, were found to be reduced at this time (4 days postinjury). We then sought to directly determine whether nerve injury results in glutamate spillover to NMDARs at dorsal horn synapses. By employing the use-dependent NMDAR blocker (±)MK-801 to block subsynaptic receptors, we found that although TBOA-induced spillover to extrasynaptic receptors trended to increased activation of these receptors after nerve injury, this was not significant compared with naïve mice. Together, these results suggest the development of neuropathic pain involves subtle changes to glutamate transporter expression and function that could contribute to neuropathic pain during excessive synaptic activity.

scholarly journals Dexmedetomidine alleviates inflammation-induced neuropathic pain by suppressing NLRP3 via activation of Nrf2

2020 ◽  
Author(s):  
Wenyan Shan ◽  
Xiaoyun Liao ◽  
Yixun Tang ◽  
Jitong Liu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Spinal Injury ◽  
Expression Patterns ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Rat Models ◽  
Withdrawal Threshold ◽  
Cord Injury

Abstract Objective: To investigate the mechanism of dexmedetomidine (DEX) involving Nrf2-dependent inhibition of NLRP3 in relieving neuropathic pain in chronic constriction injury (CCI) rat models.Methods: The CCI rat models were constructed through sciatic nerve ligation. The CCI rats were treated with DEX, Nrf2 inhibitor (ML385), NLRP3 antagonist (MCC950) and NLRP3 activator (Nigericin). Mechanical withdrawal threshold (MWT) was measured to test the pain sensitivity of CCI rats. H&E staining detected spinal injury of the rats and TUNEL staining was applied to test apoptosis in the spinal cords. ELISA measured the expressions of inflammatory factors. The expressions of Nrf2 and NLRP3 were also detected.Results: Decreased MWT, enhanced spinal cord injury, promoted apoptosis and increased inflammatory factors were detected in CCI rats. The expressions of the above indicators were retraced in DEX-treated CCI rats. Increased MWT, reduced spinal cord injury, inhibited apoptosis and decreased inflammatory factors were detected in rats treated with MCC950 or ML385 while opposite expression patterns were found in rats treated with Nigericin. The expressions of these indicators were retraced in both DEX+ML385 group and MCC950+ML385 group compared to ML385 group and MCC950 group respectively.Conclusion: DEX reduces neuropathic pain of CCI rats by suppressing NLRP3 through activation of Nrf2.

scholarly journals Differences in Gene Expression between the Classical and El Tor Biotypes of Vibrio cholerae O1

2006 ◽  
Vol 74 (6) ◽  
pp. 3633-3642 ◽  
Author(s):  
Sinem Beyhan ◽  
Anna D. Tischler ◽  
Andrew Camilli ◽  
Fitnat H. Yildiz
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Deletion Mutant ◽  
Large Fraction ◽  
Expression Patterns ◽  
Virulence Gene ◽  
Differentially Expressed ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
El Tor

ABSTRACT Differences in whole-genome expression patterns between the classical and El Tor biotypes of Vibrio cholerae O1 were determined under conditions that induce virulence gene expression in the classical biotype. A total of 524 genes (13.5% of the genome) were found to be differentially expressed in the two biotypes. The expression of genes encoding proteins required for biofilm formation, chemotaxis, and transport of amino acids, peptides, and iron was higher in the El Tor biotype. These gene expression differences may contribute to the enhanced survival capacity of the El Tor biotype in environmental reservoirs. The expression of genes encoding virulence factors was higher in the classical than in the El Tor biotype. In addition, the vieSAB genes, which were originally identified as regulators of ctxA transcription, were expressed at a fivefold higher level in the classical biotype. We determined the VieA regulon in both biotypes by transcriptome comparison of wild-type and vieA deletion mutant strains. VieA predominantly regulates gene expression in the classical biotype; 401 genes (10.3% of the genome), including those encoding proteins required for virulence, exopolysaccharide biosynthesis, and flagellum production as well as those regulated by σE, are differentially expressed in the classical vieA deletion mutant. In contrast, only five genes were regulated by VieA in the El Tor biotype. A large fraction (20.8%) of the genes that are differentially expressed in the classical versus the El Tor biotype are controlled by VieA in the classical biotype. Thus, VieA is a major regulator of genes in the classical biotype under virulence gene-inducing conditions.

scholarly journals Expression of Genes Encoding Late Nodulins Characterized by a Putative Signal Peptide and Conserved Cysteine Residues Is Reduced in Ineffective Pea Nodules

2002 ◽  
Vol 15 (2) ◽  
pp. 129-137 ◽  
Author(s):  
Takashi Kato ◽  
Kazuya Kawashima ◽  
Masami Miwa ◽  
Yoshifumi Mimura ◽  
Masanori Tamaoki ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Expression Patterns ◽  
Nodule Development ◽  
Northern Analysis ◽  
Cysteine Residues ◽  
Nitrogen Fixing ◽  
Putative Signal Peptide ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Nodulin Genes

Five nodulin genes, PsN1, PsN6, PsN314, PsN335, and PsN466, with reduced expression in ineffective nodules on the pea (Pisum sativum) mutant E135 (sym13) were characterized. They encode small polypeptides containing a putative signal peptide and conserved cysteine residues and show homology to the nodulins PsENOD3/14 and PsNOD6. For each gene, multiple bands were detected by genomic Southern analysis. Northern analysis showed that all five genes were expressed exclusively in nodules and that their temporal expression patterns were similar to that of the leghemoglobin (Lb) gene during nodule development. Their transcripts were localized predominantly from the interzone II–III to the distal part of nitrogen-fixing zone III in effective nodules, resembling the Lb gene. However, transcripts in ineffective E135 nodules were localized in narrower regions than those in the effective nodules. These results indicate that these nodulins are abundant in pea nodules and that their successive expression during nodule development is associated with nitrogen-fixing activity.

scholarly journals Transcriptional Modulation of Genes Encoding Structural Characteristics of Differentiating Enterocytes During Development of a Polarized Epithelium In Vitro

2007 ◽  
Vol 18 (11) ◽  
pp. 4261-4278 ◽  
Author(s):  
Jennifer M. Halbleib ◽  
Annika M. Sääf ◽  
Patrick O. Brown ◽  
W. James Nelson
Keyword(s):  
Gene Expression ◽  
Cell Polarity ◽  
Structural Characteristics ◽  
Expression Patterns ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Functional Features ◽  
Cell Cell

Although there is considerable evidence implicating posttranslational mechanisms in the development of epithelial cell polarity, little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized the temporal program of gene expression during cell–cell adhesion–initiated polarization of human Caco-2 cells in tissue culture, which develop structural and functional polarity similar to that of enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts between neighboring cells. Expression of genes involved in cell proliferation was down-regulated concomitant with induction of genes necessary for functional specialization of polarized epithelial cells. Transcriptional up-regulation of these latter genes correlated with formation of important structural and functional features in enterocyte differentiation and establishment of structural and functional cell polarity; components of the apical microvilli were induced as the brush border formed during polarization; as barrier function was established, expression of tight junction transmembrane proteins peaked; transcripts encoding components of the apical, but not the basal-lateral trafficking machinery were increased during polarization. Coordinated expression of genes encoding components of functional cell structures were often observed indicating temporal control of expression and assembly of multiprotein complexes.

scholarly journals PD-L1 Improves Motor Function and Alleviates Neuropathic Pain in Male Mice After Spinal Cord Injury by Inhibiting MAPK Pathway

2021 ◽  
Author(s):  
Jiangang Shi ◽  
FanQi Kong ◽  
Kaiqiang Sun ◽  
Jian Zhu ◽  
FuDong Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Inflammatory Response ◽  
Mapk Pathway ◽  
Expression Patterns ◽  
Motor Dysfunction ◽  
Locomotor Recovery ◽  
Cord Injury

Abstract Background Traumatic spinal cord injury (SCI) causes severe motor dysfunction and persistent central neuropathic pain (Nep) that remains uncured yet. Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and contributes to the immune-suppressive in tumor microenvironment, and the role of PD-L1 in regulating inflammatory response and Nep after SCI remains unclear. A growing amount of research has begun to investigate the effect of PD-L1 on macrophages and microglia. Considering the pivotal role of macrophages/microglia in the inflammatory response after SCI, we tested the hypothesis that PD-L1 improved the recovery of locomotor and sensory functions after SCI through macrophages and microglia. Methods The mice SCI model was employed to determine the changes in expression patterns of PD-L1. Meanwhile, we constructed PD-L1 knockout mice to observe differences in functional recovery and phenotypes of macrophages/microglia post-SCI. Results In present study, PD-L1 was significantly upregulated after SCI and highly expressed on macrophages/microglia. PD-L1 knockout (KO) mice showed poor locomotor recovery and serious pathological pain compared with wild-type (WT) mice. Furthermore, deletion of PD-L1 significantly increased the polarization of M1-like macrophages/microglia. Mechanistic analysis revealed that PD-L1 may improve functional outcomes following SCI by inhibiting phosphorylation of p38 and ERK1/2. Conclusions Our observations implicate the involvement of PD-L1 in recovery of SCI and provide a new treatment strategy for prevention and treatment of this traumatic condition.

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