Different effects of strength and endurance exercise training on COX-2 and mPGES expression in mouse brain are independent of peripheral inflammation

J Appl Physiol (1985). 2016 Jul 1;121(1):248-54. doi: 10.1152/japplphysiol.00284.2016. Epub 2016 Jun 9.


Acute endurance exercise has been shown to modulate cyclooxygenase (COX)-2 expression, which is suggested to affect neuronal plasticity and learning. Here, we investigated the effect of regular strength and endurance training on cerebral COX-2 expression, inflammatory markers in the brain, and circulating cytokines. Male C57BL/6N mice were assigned to either a sedentary control group (CG), an endurance training group (EG; treadmill running for 30 min/day, 5 times/wk, 10 wk), or a strength training group (SG; strength training by isometric holding, same duration as EG). Four days after the last bout of exercise, blood and brain were collected and analyzed using real-time PCR, Western blot, and a multiplexed immunoassay. In EG, COX-2 mRNA expression in the cortex/hippocampus increased compared with CG. A significant increase of COX-2 protein levels was observed in both cortex/hippocampus and hypothalamus of mice from the SG. Nuclear factor (NF)κB protein levels were significantly increased in mice from both exercise groups (hypothalamus). A significant increase in the expression of microsomal prostaglandin E synthase (mPGES), an enzyme downstream of COX-2, was found in the hypothalamus of both the EG and SG. While most inflammatory factors, like IL-1α, IL-18, and IL-2, decreased after training, a positive association was found between COX-2 mRNA expression (cortex/hippocampus) and plasma IL-6 in the EG. Taken together, this study demonstrates that both endurance as well as strength training induces COX-2 expression in the cortex/hippocampus and hypothalamus of mice. A potential mediator of COX-2 expression after training might be circulating interleukin (IL)-6. However, further research is necessary to elucidate the role of inflammatory pathways on brain plasticity after training.

Keywords: cyclooxygenase-2; cytokines; microsomal PGE synthase; prostaglandins; resistance exercise.

MeSH terms

  • Animals
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / physiopathology
  • Cyclooxygenase 2 / metabolism*
  • Cytokines / metabolism
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Physical Conditioning, Animal / physiology*
  • Physical Endurance / physiology*
  • Prostaglandin-E Synthases / metabolism*
  • RNA, Messenger / metabolism
  • Resistance Training / methods
  • Running / physiology


  • Cytokines
  • Interleukin-6
  • NF-kappa B
  • RNA, Messenger
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Prostaglandin-E Synthases