Department of Neurology, Toxicology & Neuroscience Louisiana State University Health Sciences Center, Shreveport, LA, USA.
Department of Cellular Biology and Anatomy, Toxicology & Neuroscience Louisiana State University Health Sciences Center, Shreveport, LA, USA.
Prostaglandins Leukot Essent Fatty Acids. 2021 Feb;165:102227. doi: 10.1016/j.plefa.2020.102227. Epub 2020 Dec 17.
We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator released from the sympathetic ganglion with vasoactive properties. Post-treatment with PAME can enhance cortical cerebral blood flow and functional learning and memory, while inhibiting neuronal cell death in the CA1 region of the hippocampus under pathological conditions (i.e. cerebral ischemia). Since mechanisms underlying PAME-mediated neuroprotection remain unclear, we investigated the possible neuroprotective mechanisms of PAME after 6 min of asphyxial cardiac arrest (ACA, an animal model of global cerebral ischemia). Our results from capillary-based immunoassay (for the detection of proteins) and cytokine array suggest that PAME (0.02 mg/kg) can decrease neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba1, a specific marker for microglia/macrophage activation) and inflammatory cytokines after cardiopulmonary resuscitation. Additionally, the mitochondrial oxygen consumption rate (OCR) and respiratory function in the hippocampal slices were restored following ACA (via Seahorse XF24 Extracellular Flux Analyzer) suggesting that PAME can ameliorate mitochondrial dysfunction. Finally, hippocampal protein arginine methyltransferase 1 (PRMT1) and PRMT8 are enhanced in the presence of PAME to suggest a possible pathway of methylated fatty acids to modulate arginine-based enzymatic methylation. Altogether, our findings suggest that PAME can provide neuroprotection in the presence of ACA to alleviate neuroinflammation and ameliorate mitochondrial dysfunction.
我们之前发现，棕榈酸甲酯（PAME）是一种从交感神经节释放的具有血管活性的强效血管舒张剂。在病理条件下（即脑缺血），PAME 处理后可以增强皮质脑血流和功能学习记忆，同时抑制海马 CA1 区神经元细胞死亡。由于 PAME 介导的神经保护作用的机制尚不清楚，我们研究了 PAME 在 6 分钟窒息性心脏骤停（ACA，全脑缺血动物模型）后的可能神经保护机制。我们基于毛细管的免疫测定（用于检测蛋白质）和细胞因子阵列的结果表明，PAME（0.02mg/kg）可以降低神经炎症标志物，如离子钙结合衔接蛋白 1（Iba1，小胶质细胞/巨噬细胞活化的特异性标志物）和炎性细胞因子，在心肺复苏后。此外，海马切片中的线粒体耗氧率（OCR）和呼吸功能在 ACA 后得到恢复（通过 Seahorse XF24 细胞外通量分析仪），表明 PAME 可以改善线粒体功能障碍。最后，在存在 PAME 的情况下，海马蛋白精氨酸甲基转移酶 1（PRMT1）和 PRMT8 增强，表明甲基化脂肪酸可能通过调节基于精氨酸的酶甲基化来发挥作用。总之，我们的研究结果表明，PAME 可以在 ACA 存在的情况下提供神经保护，减轻神经炎症并改善线粒体功能障碍。
