Dopamine inhibits pyroptosis and attenuates secondary damage after spinal cord injury in female mice

Neurosci Lett. 2023 Jan 1:792:136935. doi: 10.1016/j.neulet.2022.136935. Epub 2022 Oct 25.

Abstract

Background: An excessive inflammatory response accompanies the pathogenesis of spinal cord injury (SCI) and has been found to be promoted by inflammasomes in a variety of disease models. Dopamine is a neurotransmitter that also regulates nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome-dependent neuroinflammation. However, little is known regarding the effects and molecular mechanisms underlying the role of dopamine in SCI.

Methods: Functional recovery in mice was assessed with the Basso Mouse Scale (BMS). Neuronal loss was evaluated with immunochemical staining of NeuN. Pyroptosis was assessed with immunofluorescence staining, flow cytometry, western blotting, and cell viability and cytotoxicity assays.

Results: Dopamine was significantly associated with enhanced locomotor recovery after SCI, and with decreased NLRP3 inflammasome activation, pyroptosis, neuronal loss and pro-inflammatory cytokine levels. In vitro data suggested that dopamine suppressed NLRP3 inflammasome activation and pyroptosis, and decreased pro-inflammatory cytokine levels.

Conclusions: Dopamine may be a novel approach for alleviating secondary damage after SCI.

Keywords: Dopamine; Inflammasome; Inflammatory response; Neuronal loss; Pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / pharmacology
  • Dopamine / pharmacology
  • Female
  • Inflammasomes
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Pyroptosis* / physiology
  • Spinal Cord / pathology
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / pathology

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Dopamine
  • Cytokines