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.

Reduced blood‐brain barrier expression of fatty acid‐binding protein 5 is associated with increased vulnerability of APP/PS1 mice to cognitive deficits from low omega‐3 fatty acid diets

“…Given that FABP5 has been shown to be up‐regulated by DHA (Figueroa et al . ), the reduced FABP5 at the BBB in APP/PS1 mice could also be secondary to lower plasma levels of DHA. Indeed, lower DHA levels in the liver have been reported in 3‐month‐old APP/PS1 mice compared to WT littermates (Perez et al .…”

Dietary docosahexaenoic acid supplementation enhances expression of fatty acid‐binding protein 5 at the blood–brain barrier and brain docosahexaenoic acid levels

“…A 1.7‐fold increase in brain microvascular FABP5 expression was identified in mice fed the DHA‐enriched diet, compared to the control group, which is in agreement with a previous study, where spinal cord FABP5 gene expression elevated twofold in rats fed a DHA‐enriched diet for 8 weeks (Figueroa et al . ). The higher fold increase in FABP5 expression observed in the mouse dietary intervention study than the in vitro study could be explained by the longer term of exposure to higher levels of DHA.…”

“…Spinal cord FABP5 gene expression elevated twofold in rats fed a DHA‐enriched diet for 8 weeks (Figueroa et al . ). Therefore, DHA has the potential to up‐regulate BBB expression of FABP5 and help to facilitate its own transport across the BBB.…”

Identifying the Biomarkers of Spinal Cord Injury and the effects of Neurotrophin-3 Based on MicroRNA and mRNA Signature

“…Former study has demonstrated that the ketogenic diet improves forelimb motor function after spinal cord injury in rodents [17]. And Omega-3 polyunsaturated fatty acids could promote functional recovery in rats undergoing spinal cord injury [18]. So, GHSR could be related to neurological injury and the neurotrophin-3 treatment by regulating the cellular ketone metabolic process and fatty acid metabolic process.…”