title: 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.affiliation: Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Agrawal
authors.affiliation: Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Ethika
authors.initials: E
authors.lastname: Tyagi
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vergnes
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
authors.affiliation: Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA 90095, USA; Department of Neurosurgery, UCLA Brain Injury Research Center, Los Angeles, CA 90095, USA. Electronic address: fgomezpi@ucla.edu.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez-Pinilla
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology; D001930:Brain Injuries / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D004734:Energy Metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D006706:Homeostasis; D008928:Mitochondria / Q000502:physiology; D009473:Neuronal Plasticity; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000032:analysis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015525:Fatty Acids, Omega-3; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D020813:Receptor, trkB
keywords: Anxiety; Brain Trauma; Metabolism; Mitochondria; Omega-3; Plasticity