DUBOVÝ, Petr, Ivana HRADILOVÁ SVÍŽENSKÁ, Václav BRÁZDA and Marek JOUKAL. Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion. International Journal of Molecular Sciences. Basel: MDPI, 2021, vol. 22, No 14, p. 1-17. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms22147446.
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Basic information
Original name Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion
Authors DUBOVÝ, Petr (203 Czech Republic, guarantor, belonging to the institution), Ivana HRADILOVÁ SVÍŽENSKÁ (203 Czech Republic, belonging to the institution), Václav BRÁZDA (203 Czech Republic, belonging to the institution) and Marek JOUKAL (203 Czech Republic, belonging to the institution).
Edition International Journal of Molecular Sciences, Basel, MDPI, 2021, 1422-0067.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 6.208
RIV identification code RIV/00216224:14110/21:00119177
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.3390/ijms22147446
UT WoS 000676311100001
Keywords in English sciatic nerve; compression; transection; mitochondrial DNA; the endoplasmic reticulum; early endosomes; axon regeneration
Tags 14110514, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 5/4/2022 13:42.
Abstract
One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)-the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NF kappa B) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG. The relationship of TLR9 to the induction of a pro-regenerative state in the cervical DRG neurons was confirmed by the shorter lengths of regenerated axons distal to ulnar nerve crush following a previous sciatic nerve lesion and intrathecal chloroquine injection compared with control rats. The results suggest that a systemic innate immune reaction not only triggers the regenerative state of axotomized DRG neurons but also induces a pro-regenerative state further along the neural axis after unilateral nerve injury.
Links
GA16-08508S, research and development projectName: Zvýšení endogenního regeneračního programu a jeho aktivace zprostředkovaná cytokiny/chemokiny v neuronech ganglií bez spojení s poškozeným nervem (Acronym: ERP)
Investor: Czech Science Foundation
MUNI/A/1520/2020, interní kód MUName: Změny ve strukturách nervové soustavy v reakci na poškození
Investor: Masaryk University
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