Figueroa Johnny D, Serrano-Illan Miguel, Licero Jenniffer, Cordero Kathia, Miranda Jorge D, De Leon Marino
1 Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine , Loma Linda, California.
2 Physiology Department, University of Puerto Rico Medical Sciences Campus , San Juan, Puerto Rico .
J Neurotrauma. 2016 Aug 1;33(15):1436-49. doi: 10.1089/neu.2015.4186. Epub 2016 Mar 29.
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.
ω-3多不饱和脂肪酸（n-3 PUFAs）可促进脊髓损伤（SCI）大鼠的功能恢复。然而，n-3 PUFAs与神经修复反应相关的确切分子机制尚不清楚。本研究的目的是确定挫伤性SCI后脂肪酸结合蛋白5（FABP5）的时空表达，并研究该蛋白是否在n-3 PUFA介导的SCI后功能恢复中发挥作用。我们发现，与假手术大鼠相比，SCI导致损伤后7天（dpi）脊髓中FABP5 mRNA水平（556±187%）和蛋白表达（518±195%）显著上调。基于代谢组学的脂质分析显示，这种上调与损伤脊髓中脂肪酸代谢的显著改变同时发生。特别是，我们发现在7 dpi时n-3系列PUFAs水平升高，尤其是二十二碳六烯酸（DHA；22:6 n-3）和二十碳五烯酸（EPA；20:5 n-3）。食用富含DHA和EPA饮食的动物在7 dpi时FABP5 mRNA水平显著上调。免疫荧光显示，假手术大鼠脊髓腹侧灰质NeuN(+)神经元中FABP5的基础免疫反应性较低。SCI导致神经胶质细胞（GFAP(+)、APC(+)和NG2(+)）和前体细胞（DCX(+)、巢蛋白(+)）中FABP5的强烈诱导。我们发现，连续鞘内注射小干扰RNA（2μg）沉默FABP5会损害SCI后自发的旷场运动。此外，在7 dpi时，给予FABP5 siRNA会阻碍DHA改善功能恢复的有益作用。总之，我们的研究结果表明，FABP5可能是促进SCI后DHA细胞摄取、转运和/或代谢的重要因素。鉴于n-3 PUFAs在改善功能恢复方面的有益作用，我们认为FABP5是损伤脊髓基本修复机制的重要贡献者。
