Drosophila model for in vivo pharmacological analgesia research

Manev, Hari; Dimitrijević, Nikola

doi:10.1016/j.ejphar.2004.03.030

Cited by 39 publications

(34 citation statements)

References 7 publications

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“…[16][17][18][19] Most importantly, Drosophila genetics allows us to specifically knockdown genes in nociceptive sensory neurons and thus avoid any confounding developmental effects on other tissues such as the central nervous system. 20,21 In Drosophila, 4 PRDM family members containing a PRDM/SET domain have been found, namely, CG43347, CG13296, Hamlet and Blimp1. Among these 4, we used RNA interference to knockdown expression of Hamlet and Blimp1 (Fig.…”

Section: Introduction and Resultsmentioning

confidence: 99%

The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception

et al. 2015

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These authors contributed equally to this work.Keywords: Hamlet, nociception, PRDM12, sensory neurons, TRHDE Abbreviation: PRDM12, PR homology domain-containing member 12; HSAN, hereditary and sensory autonomic neuropathy; TRHDE, tyrotropin-releasing hormone degrading enzyme; RA, retinoic acid; Brn3d, brain 3d; Tlx3, T-cell leukemia homeobox 3; Hmx3, H6 family homeobox 3; Drgx, dorsal root ganglia homeobox; Sncg, Synuclein Gamma (Breast Cancer-Specific Protein 1); En1, engrailed-1; RT-qPCR, real-time quantitative polymerase chain reaction; MO, morpholino oligonucleotide; ChIP, chromatin immunoprecipitation; S1PR1, Sphi8ngosine-1-phosphate receptor 1; CGNL1, cyclin L1; IL1R1, interleukin 1 receptor type 1; TRH(DE), tryrotropin-releasing hormone degrading enzyme; pCMV6, plasmid cytomegalovirus; DDK, DYKDDDDK epitope; GAPDH, glyceraldehyde 3-phospate dehydrogenase; NBT/BCIP, nitro blue tetrazolium / 5-bromo-4-chloro-3-indolyl-phosphate; SET, Su(var)3-9 and 'Enhancer of zeste'; PDB, protein data base; HEK293, human embryonic kidney cell 293; PBS, phosphate buffered saline; DAPI, 4 0 ,6-diamidino-2-phenylindole; GFP, green fluorescent protein; BSA, bovine serum albumin; HRP, horseraddish peroxidase; ECL, enhanced chemiluminescence; FPKM, fragments per kilobase exon; FDR, false discovery rate; GEO, gene expression omnibus; PMID, pubmed identification.PR homology domain-containing member 12 (PRDM12) belongs to a family of conserved transcription factors implicated in cell fate decisions. Here we show that PRDM12 is a key regulator of sensory neuronal specification in Xenopus. Modeling of human PRDM12 mutations that cause hereditary sensory and autonomic neuropathy (HSAN) revealed remarkable conservation of the mutated residues in evolution. Expression of wild-type human PRDM12 in Xenopus induced the expression of sensory neuronal markers, which was reduced using various human PRDM12 mutants. In Drosophila, we identified Hamlet as the functional PRDM12 homolog that controls nociceptive behavior in sensory neurons. Furthermore, expression analysis of human patient fibroblasts with PRDM12 mutations uncovered possible downstream target genes. Knockdown of several of these target genes including thyrotropin-releasing hormone degrading enzyme (TRHDE) in Drosophila sensory neurons resulted in altered cellular morphology and impaired nociception. These data show that PRDM12 and its functional fly homolog Hamlet are evolutionary conserved master regulators of sensory neuronal specification and play a critical role in pain perception. Our data also uncover novel pathways in multiple species that regulate evolutionary conserved nociception.

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Section: Introduction and Resultsmentioning

confidence: 99%

The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception

et al. 2015

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“…No control vehicle-injected flies passed through the tunnel at 60 8C, whereas 3-APMPA dose-dependently allows the heat barrier to be crossed. At 42 8C, 27.5% of control flies pass through; 2 pmol/fly of 3-APMPA, a dose ineffective at 60 8C, allowed 57.5% of the flies to pass the 42 8C barrier (Manev and Dimitrijevic, 2004). These experiments demonstrate that drugs active as analgesics in mammals produce antinociception-like effects in adult Drosophila and confirmed that fruit flies can be used in pharmacological pain research.…”

Section: Pharmacological Antinociception In Fliesmentioning

confidence: 68%

Fruit flies for anti-pain drug discovery

Manev

Dimitrijević

2005

Life Sciences

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“…Fruit flies ( Drosophila melanogaster ) have been used in genetics studies and neuropharmacology for a long time, and they recently have become a powerful model organism for pharmacological pain research [92]. In response to the touch of a probe heated above 38°C, Drosophila larvae produce a stereotypical rolling behavior, unlike the response to an unheated probe.…”

Section: Nature and Painmentioning

confidence: 99%

Nature and Nurture of Human Pain

Belfer

2013

Scientifica

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Humans are very different when it comes to pain. Some get painful piercings and tattoos; others can not stand even a flu shot. Interindividual variability is one of the main characteristics of human pain on every level including the processing of nociceptive impulses at the periphery, modification of pain signal in the central nervous system, perception of pain, and response to analgesic strategies. As for many other complex behaviors, the sources of this variability come from both nurture (environment) and nature (genes). Here, I will discuss how these factors contribute to human pain separately and via interplay and how epigenetic mechanisms add to the complexity of their effects.

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Drosophila model for in vivo pharmacological analgesia research

Cited by 39 publications

References 7 publications

The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception

The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception

Fruit flies for anti-pain drug discovery

Nature and Nurture of Human Pain

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