title: Fatty Acid Binding Protein 5 Modulates Docosahexaenoic Acid-Induced Recovery in Rats Undergoing Spinal Cord Injury.
abstract: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) promote functional recovery in rats undergoing spinal cord injury (SCI). However, the precise molecular mechanism coupling n-3 PUFAs to neurorestorative responses is not well understood. The aim of the present study was to determine the spatiotemporal expression of fatty acid binding protein 5 (FABP5) after contusive SCI and to investigate whether this protein plays a role in n-3 PUFA-mediated functional recovery post-SCI. We found that SCI resulted in a robust spinal cord up-regulation in FABP5 mRNA levels (556 ± 187%) and protein expression (518 ± 195%), when compared to sham-operated rats, at 7 days post-injury (dpi). This upregulation coincided with significant alterations in the metabolism of fatty acids in the injured spinal cord, as revealed by metabolomics-based lipid analyses. In particular, we found increased levels of the n-3 series PUFAs, particularly docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA; 20:5 n-3) at 7 dpi. Animals consuming a diet rich in DHA and EPA exhibited a significant upregulation in FABP5 mRNA levels at 7 dpi. Immunofluorescence showed low basal FABP5 immunoreactivity in spinal cord ventral gray matter NeuN(+) neurons of sham-operated rats. SCI resulted in a robust induction of FABP5 in glial (GFAP(+), APC(+), and NG2(+)) and precursor cells (DCX(+), nestin(+)). We found that continuous intrathecal administration of FABP5 silencing with small interfering RNA (2 μg) impaired spontaneous open-field locomotion post-SCI. Further, FABP5 siRNA administration hindered the beneficial effects of DHA to ameliorate functional recovery at 7 dpi. Altogether, our findings suggest that FABP5 may be an important player in the promotion of cellular uptake, transport, and/or metabolism of DHA post-SCI. Given the beneficial roles of n-3 PUFAs in ameliorating functional recovery, we propose that FABP5 is an important contributor to basic repair mechanisms in the injured spinal cord.
authors.affiliation: 1 Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine , Loma Linda, California.
authors.forename: Johnny D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: 1 Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine , Loma Linda, California.
authors.forename: Miguel
authors.initials: M
authors.lastname: Serrano-Illan
authors.affiliation: 1 Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine , Loma Linda, California.
authors.forename: Jenniffer
authors.initials: J
authors.lastname: Licero
authors.affiliation: 1 Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine , Loma Linda, California.
authors.forename: Kathia
authors.initials: K
authors.lastname: Cordero
authors.affiliation: 2 Physiology Department, University of Puerto Rico Medical Sciences Campus , San Juan, Puerto Rico .
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Miranda
authors.affiliation: 1 Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine , Loma Linda, California.
authors.forename: Marino
authors.initials: M
authors.lastname: De Leon
mesh_terms: D000818:Animals; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D000089662:Doublecortin Protein; D005136:Eye Proteins / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005136:Eye Proteins; C107356:Fabp5 protein, rat; D050556:Fatty Acid-Binding Proteins; D009419:Nerve Tissue Proteins; D004281:Docosahexaenoic Acids
keywords: DHA; locomotion; n-3 fatty acids; repair; spinal cord injury