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

J 2021

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

DUBOVÝ, Petr, Ivana HRADILOVÁ SVÍŽENSKÁ, Václav BRÁZDA and Marek JOUKAL

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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 project

Name: 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 MU

Name: Změny ve strukturách nervové soustavy v reakci na poškození

Investor: Masaryk University

Citovat

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.

@article{1789477,
   author = {Dubový, Petr and Hradilová Svíženská, Ivana and Brázda, Václav and Joukal, Marek},
   article_location = {Basel},
   article_number = {14},
   doi = {http://dx.doi.org/10.3390/ijms22147446},
   keywords = {sciatic nerve; compression; transection; mitochondrial DNA; the endoplasmic reticulum; early endosomes; axon regeneration},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {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},
   url = {https://www.mdpi.com/1422-0067/22/14/7446},
   volume = {22},
   year = {2021}
}

TY  - JOUR
ID  - 1789477
AU  - Dubový, Petr - Hradilová Svíženská, Ivana - Brázda, Václav - Joukal, Marek
PY  - 2021
TI  - 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
JF  - International Journal of Molecular Sciences
VL  - 22
IS  - 14
SP  - 1-17
EP  - 1-17
PB  - MDPI
SN  - 14220067
KW  - sciatic nerve
KW  - compression
KW  - transection
KW  - mitochondrial DNA
KW  - the endoplasmic reticulum
KW  - early endosomes
KW  - axon regeneration
UR  - https://www.mdpi.com/1422-0067/22/14/7446
N2  - 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.
ER  -

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. \textit{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.

Detailed Information on Publication Record