title: Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury.
abstract: Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome.
authors.affiliation: Center for Health Disparities and Molecular Medicine and Departments of Basic Sciences and Pathology and Human Anatomy, Loma Linda University, Loma Linda, California, USA.
authors.forename: Johnny D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Kathia
authors.initials: K
authors.lastname: Cordero
authors.forename: Miguel S
authors.initials: MS
authors.lastname: Llán
authors.forename: Marino
authors.initials: M
authors.lastname: De Leon
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage / Q000627:therapeutic use*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids