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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; Hradilová-Svízenská, Ivana; Brázda, Václav; Joukal, Marek.
Afiliação
  • Dubový P; Cellular and Molecular Research Group, Department of Anatomy, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500 Brno, Czech Republic.
  • Hradilová-Svízenská I; Cellular and Molecular Research Group, Department of Anatomy, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500 Brno, Czech Republic.
  • Brázda V; Cellular and Molecular Research Group, Department of Anatomy, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500 Brno, Czech Republic.
  • Joukal M; Cellular and Molecular Research Group, Department of Anatomy, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500 Brno, Czech Republic.
Int J Mol Sci ; 22(14)2021 Jul 12.
Article em En | MEDLINE | ID: mdl-34299065
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 (NFκB) 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuropatia Ciática / Fator de Transcrição STAT3 / Receptor Toll-Like 9 / Gânglios Espinais / Imunidade Inata / Neurônios Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neuropatia Ciática / Fator de Transcrição STAT3 / Receptor Toll-Like 9 / Gânglios Espinais / Imunidade Inata / Neurônios Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article