Exercise facilitates the action of dietary DHA on functional recovery after brain trauma

Neuroscience. 2013 Sep 17;248:655-63. doi: 10.1016/j.neuroscience.2013.06.041. Epub 2013 Jun 28.


The abilities of docosahexaenoic acid (DHA) and exercise to counteract cognitive decay after traumatic brain injury (TBI) is getting increasing recognition; however, the possibility that these actions can be complementary remains just as an intriguing possibility. Here we have examined the likelihood that the combination of diet and exercise has the added potential to facilitate functional recovery following TBI. Rats received mild fluid percussion injury (mFPI) or sham injury and then were maintained on a diet high in DHA (1.2% DHA) with or without voluntary exercise for 12days. We found that FPI reduced DHA content in the brain, which was accompanied by increased levels of lipid peroxidation assessed using 4-hydroxy-2-hexenal (4-HHE). FPI reduced the enzymes acyl-CoA oxidase 1 (Acox1) and 17β-hydroxysteroid dehydrogenase type 4 (17β-HSD4), and the calcium-independent phospholipases A2 (iPLA2), which are involved in metabolism of membrane phospholipids. FPI reduced levels of syntaxin-3 (STX-3), involved in the action of membrane DHA on synaptic membrane expansion, and also reduced brain-derived neurotrophic factor (BDNF) signaling through its tyrosine kinase B (TrkB) receptor. These effects of FPI were optimally counteracted by the combination of DHA and exercise. Our results support the possibility that the complementary action of exercise is exerted on restoring membrane homeostasis after TBI, which is necessary for supporting synaptic plasticity and cognition. It is our contention that strategies that take advantage of the combined applications of diet and exercise may have additional effects to the injured brain.

Keywords: 17β-HSD4; 17β-hydroxysteroid dehydrogenase type 4; ANOVA; Acox1; BDNF; CTL; DHA; Exc; FAME; FPI; GC; MWZ; Morris water maze; RGD; STX-3; Sed; TBI; acyl-CoA oxidase 1; analysis of variance; calcium-independent phospholipase A2; cognition; control; docosahexaenoic acid; exercise; fatty acid methyl esters; fluid percussion injury; gas chromatography; iPLA2; omega-3 fatty acids; regular diet; sedentary; syntaxin 3; traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyl-CoA Oxidase / metabolism*
  • Animals
  • Brain Injuries / diet therapy
  • Brain Injuries / physiopathology
  • Brain Injuries / therapy*
  • Cognition / drug effects
  • Combined Modality Therapy
  • Docosahexaenoic Acids / administration & dosage*
  • Docosahexaenoic Acids / metabolism
  • Docosahexaenoic Acids / therapeutic use
  • Exercise Therapy*
  • Maze Learning / drug effects
  • Neuronal Plasticity / drug effects
  • Oxidative Stress / physiology
  • Peroxisomal Multifunctional Protein-2 / metabolism*
  • Phospholipases A2, Calcium-Independent / metabolism*
  • Qa-SNARE Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function*
  • Synapses / drug effects


  • Qa-SNARE Proteins
  • Docosahexaenoic Acids
  • Acyl-CoA Oxidase
  • Phospholipases A2, Calcium-Independent
  • Peroxisomal Multifunctional Protein-2