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 a Marek JOUKAL

Základní údaje

Originální název

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

Autoři

DUBOVÝ, Petr (203 Česká republika, garant, domácí), Ivana HRADILOVÁ SVÍŽENSKÁ (203 Česká republika, domácí), Václav BRÁZDA (203 Česká republika, domácí) a Marek JOUKAL (203 Česká republika, domácí)

Vydání

International Journal of Molecular Sciences, Basel, MDPI, 2021, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.208

Kód RIV

RIV/00216224:14110/21:00119177

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3390/ijms22147446

UT WoS

000676311100001

Klíčová slova anglicky

sciatic nerve; compression; transection; mitochondrial DNA; the endoplasmic reticulum; early endosomes; axon regeneration

Štítky

14110514, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 4. 2022 13:42, Mgr. Tereza Miškechová

Anotace

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.

Návaznosti

GA16-08508S, projekt VaV

Název: Zvýšení endogenního regeneračního programu a jeho aktivace zprostředkovaná cytokiny/chemokiny v neuronech ganglií bez spojení s poškozeným nervem (Akronym: ERP)

Investor: Grantová agentura ČR, Zvýšení endogenního regeneračního programu a jeho aktivace zprostředkovaná cytokiny/chemokiny

MUNI/A/1520/2020, interní kód MU

Název: Změny ve strukturách nervové soustavy v reakci na poškození

Investor: Masarykova univerzita, Změny ve strukturách nervové soustavy v reakci na poškození

Citovat

DUBOVÝ, Petr, Ivana HRADILOVÁ SVÍŽENSKÁ, Václav BRÁZDA a 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, roč. 22, č. 14, s. 1-17. ISSN 1422-0067. Dostupné z: 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 a 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, roč.~22, č.~14, s.~1-17. ISSN~1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms22147446.

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