Resistance physical exercise alleviates lipopolysaccharide-triggered neuroinflammation in cortex and hippocampus of rats via purinergic signaling

Neurotoxicology. 2023 Dec:99:217-225. doi: 10.1016/j.neuro.2023.10.011. Epub 2023 Oct 26.

Abstract

Resistance physical exercise has neuroprotective and anti-inflammatory effects on many known diseases and, therefore, it has been increasingly explored. The way in which this type of exercise exerts these actions is still under investigation. In this study, we aimed to analyze the enzymes and components of the purinergic system involved in the inflammatory process triggered by the P2X7R. Rats were divided into four groups: control, exercise (EX), lipopolysaccharide (LPS), and EX + LPS. The animals in the exercise groups were subjected to a 12-week ladder-climbing resistance physical exercise and received LPS after the last session for sepsis induction. Enzymes activities (NTPDase, 5'-nucleotidase, and adenosine deaminase), purinoceptors' density (P2X7R, A1, and A2A), and the levels of inflammatory indicators (pyrin domain-containing protein 3 (NLRP3), Caspase-1, interleukin (IL)- 6, IL-1B, and tumor necrosis factor (TNF) -α) were measured in the cortex and hippocampus of the animals. The results show that exercise prevented (in the both structures) the increase of: 1) nucleoside-triphosphatase (NTPDase) and 5'-nucleotidase activities; 2) P2X7R density; 3) NLRP3 and Caspase-1; and 4) IL-6, IL-1β, and TNF-α It is suggested that the purinergic system and the inflammatory pathway of P2X7R are of fundamental importance and influence the effects of resistance physical exercise on LPS-induced inflammation. Thus, the modulation of the P2X7R by resistance physical exercise offers new avenues for the management of inflammatory-related illnesses.

Keywords: Lipopolysaccharide; Neuroinflammation; Neuroprotection; P2X7 receptor; Purinergic system; Resistance physical exercise.

MeSH terms

  • 5'-Nucleotidase / metabolism
  • Animals
  • Caspases / metabolism
  • Exercise
  • Hippocampus / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides* / toxicity
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Neuroinflammatory Diseases
  • Rats
  • Receptors, Purinergic P2X7 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Lipopolysaccharides
  • 5'-Nucleotidase
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Caspases
  • Receptors, Purinergic P2X7