Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8260347 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2014 | 12 Pages |
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.
Keywords
NRFsAMPKTrkBFCCPSOD2PGC-1α7,8-DHFEPMPUFAsOCROXPHOSTFAMNeuropeptide Y1 receptorLPOSTBINPY1Rnuclear respiratory factorsperoxisome proliferator-activated receptor gamma coactivator 1-alpha7,8-DihydroxyflavoneBDNFMitochondrial DNAFPIROSTraumatic brain injuryFluid percussion injuryBrain traumadocosahexaenoic acidPolyunsaturated fatty acidsAnxietyOmega-3elevated plus mazetropomyosin receptor kinase BDHAmtDNASuperoxide dismutasemitochondrial transcription factor ABrain-derived neurotrophic factorOxidative phosphorylationMetabolismMitochondriaOxygen consumption rateLipid peroxidesadenosine monophosphate-activated protein kinasePlasticityCOIIcarbonyl cyanide-p-trifluoromethoxyphenylhydrazoneReactive oxygen species
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Authors
Rahul Agrawal, Ethika Tyagi, Laurent Vergnes, Karen Reue, Fernando Gomez-Pinilla,