Upregulation of receptors for mitochondrial damage associated molecular patterns in the dorsal root ganglia of experimental neuropathic pain models based on sciatic nerve injury

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F17%3A00101402" target="_blank" >RIV/00216224:14110/17:00101402 - isvavai.cz</a>

Výsledek na webu

<a href="https://web.kenes.com/KLead/EFIC2017Abstract/data/HtmlApp/main.html" target="_blank" >https://web.kenes.com/KLead/EFIC2017Abstract/data/HtmlApp/main.html</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Upregulation of receptors for mitochondrial damage associated molecular patterns in the dorsal root ganglia of experimental neuropathic pain models based on sciatic nerve injury

Popis výsledku v původním jazyce

Upregulation of receptors for mitochondrial damage associated molecular patterns in the dorsal root ganglia of experimental neuropathic pain models based on sciatic nerve injury Dubový P., Klusáková I., Joukal M., Hradilová-Svíženská I. Department of Anatomy, Cellular and Molecular Neurobiology Group, Faculty of Medicine, Masaryk University, Kamenice 3, 62500 Brno, Czech Republic Most frequently used experimental models of neuropathic pain (NPP) are based on chronic constriction injury (CCI) or spared nerve injury (SNI) of the rat sciatic nerve. Disintegration of mitochondria including release of mitochondrial proteins and their DNAs (mtDNAs) is present in Wallerian degeneration (WD) distal to nerve injury. N-formyl peptides released by ruptured mitochondria are ligands of the formyl-peptide receptor 2 (FPR2) and mtDNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We studied cellular distribution of FPR2 and TLR9 by immunohistochemical detection in the dorsal root ganglia (DRG) associated (L4-L5 segments) and non-associated (C6-C8 segments) with the sciatic nerve injury of both CCI and SNI models. An induction of NPP was tested by measurement of withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity. We found a low intensity of FPR2 and TLR9 immunofluorescence in DRG neurons of all populations. Unilateral CCI and SNI of the sciatic nerve induced mechanical and thermal hypersensitivity in operated hind paws. However, increased FPR2 and TLR9 immunofluorescence intensity was measured bilaterally not only in DRG of L4-L5 segments, but also in remote C6-C8 DRG. Increased expression of FPR2 and TLR9 predominantly in neuronal bodies corresponds with bilateral upregulation of inflammatory mediators (1, 2). Our results suggest that inflammatory reactions in DRG might be mediated by receptors for mitochondrial damage associated molecular patterns produced by WD. In addition, the present results provide further evidence that inflammatory reaction after unilateral sciatic nerve injury is not limited to associated DRG, but can spread alongside of neuroaxis. A contribution of induced inflammation in non-impaired neurons of remote DRG to NPP remains to be elucidated. It seems that Surviving primary injury to next impairment it 1. Dubový et al., Histochem. Cell Biol. 133, 323-337 (2010). 2. Dubový et al., J. Neuroinflamm, 10, 55 (2013). Acknowledgements. The work was supported by grant 16-08508S of The Czech Science Foundation (GACR). We thank Bc. Jitka Mikulášková, Ms. Dana Kutějová and Ms. Marta Lněníčková for their skillful technical assistance.

Název v anglickém jazyce

Upregulation of receptors for mitochondrial damage associated molecular patterns in the dorsal root ganglia of experimental neuropathic pain models based on sciatic nerve injury

Popis výsledku anglicky

Upregulation of receptors for mitochondrial damage associated molecular patterns in the dorsal root ganglia of experimental neuropathic pain models based on sciatic nerve injury Dubový P., Klusáková I., Joukal M., Hradilová-Svíženská I. Department of Anatomy, Cellular and Molecular Neurobiology Group, Faculty of Medicine, Masaryk University, Kamenice 3, 62500 Brno, Czech Republic Most frequently used experimental models of neuropathic pain (NPP) are based on chronic constriction injury (CCI) or spared nerve injury (SNI) of the rat sciatic nerve. Disintegration of mitochondria including release of mitochondrial proteins and their DNAs (mtDNAs) is present in Wallerian degeneration (WD) distal to nerve injury. N-formyl peptides released by ruptured mitochondria are ligands of the formyl-peptide receptor 2 (FPR2) and mtDNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We studied cellular distribution of FPR2 and TLR9 by immunohistochemical detection in the dorsal root ganglia (DRG) associated (L4-L5 segments) and non-associated (C6-C8 segments) with the sciatic nerve injury of both CCI and SNI models. An induction of NPP was tested by measurement of withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity. We found a low intensity of FPR2 and TLR9 immunofluorescence in DRG neurons of all populations. Unilateral CCI and SNI of the sciatic nerve induced mechanical and thermal hypersensitivity in operated hind paws. However, increased FPR2 and TLR9 immunofluorescence intensity was measured bilaterally not only in DRG of L4-L5 segments, but also in remote C6-C8 DRG. Increased expression of FPR2 and TLR9 predominantly in neuronal bodies corresponds with bilateral upregulation of inflammatory mediators (1, 2). Our results suggest that inflammatory reactions in DRG might be mediated by receptors for mitochondrial damage associated molecular patterns produced by WD. In addition, the present results provide further evidence that inflammatory reaction after unilateral sciatic nerve injury is not limited to associated DRG, but can spread alongside of neuroaxis. A contribution of induced inflammation in non-impaired neurons of remote DRG to NPP remains to be elucidated. It seems that Surviving primary injury to next impairment it 1. Dubový et al., Histochem. Cell Biol. 133, 323-337 (2010). 2. Dubový et al., J. Neuroinflamm, 10, 55 (2013). Acknowledgements. The work was supported by grant 16-08508S of The Czech Science Foundation (GACR). We thank Bc. Jitka Mikulášková, Ms. Dana Kutějová and Ms. Marta Lněníčková for their skillful technical assistance.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA16-08508S" target="_blank" >GA16-08508S: Zvýšení endogenního regeneračního programu a jeho aktivace zprostředkovaná cytokiny/chemokiny v neuronech ganglií bez spojení s poškozeným nervem</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů