Coupling energy homeostasis with a mechanism to support plasticity in brain trauma.

Abstract

Metabolic dysfunction occurring after traumatic brain injury (TBI) is an important risk factor for the development of psychiatric illness. In the present study, we utilized an omega-3 diet during early life as a metabolic preconditioning to alter the course of TBI during adulthood. TBI animals under omega-3 deficiency were more prone to alterations in energy homeostasis (adenosine monophosphate-activated protein kinase; AMPK phosphorylation and cytochrome C oxidase II; COII levels) and mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PGC-1α and mitochondrial transcription factor A; TFAM). A similar response was found for brain-derived neurotrophic factor (BDNF) and its signaling through tropomyosin receptor kinase B (TrkB). The results from in vitro studies showed that 7,8-dihydroxyflavone (7,8-DHF), a TrkB receptor agonist, upregulates the levels of biogenesis activator PGC-1α, and CREB phosphorylation in neuroblastoma cells suggesting that BDNF-TrkB signaling is pivotal for engaging signals related to synaptic plasticity and energy metabolism. The treatment with 7,8-DHF elevated the mitochondrial respiratory capacity, which emphasizes the role of BDNF-TrkB signaling as mitochondrial bioenergetics stimulator. Omega-3 deficiency worsened the effects of TBI on anxiety-like behavior and potentiated a reduction of anxiolytic neuropeptide Y1 receptor (NPY1R). These results highlight the action of metabolic preconditioning for building long-term neuronal resilience against TBI incurred during adulthood. Overall, the results emphasize the interactive action of metabolic and plasticity signals for supporting neurological health.

• Authors: Rahul Agrawal, Ethika Tyagi, Laurent Vergnes, Karen Reue, Fernando Gomez-Pinilla
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1842 Issue 4 Pg. 535-46 (Apr 2014) ISSN: 0006-3002 [Print] Netherlands
• PMID: 24345766 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013. Published by Elsevier B.V.

Chemical References

• Brain-Derived Neurotrophic Factor
• Fatty Acids, Omega-3
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, rat
• Transcription Factors
• Receptor, trkB

Topics

• Animals
• Anxiety (etiology)
• Brain Injuries (metabolism)
• Brain-Derived Neurotrophic Factor (physiology)
• Energy Metabolism
• Fatty Acids, Omega-3 (administration & dosage)
• Female
• Homeostasis
• Mitochondria (physiology)
• Neuronal Plasticity
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Rats
• Rats, Sprague-Dawley
• Receptor, trkB (physiology)
• Signal Transduction
• Transcription Factors (analysis)