PDF(Pubmed)
Abstract：
Exposure to the neurotoxin trimethyltin (TMT) selectively induces hippocampal neuronal injury and astrocyte activation accompanied with resultant neuroinflammation, which causes severe behavioral, cognitive, and memory impairment. A large body of evidence suggests that flaxseed oil (FSO), as one of the richest sources of essential omega-3 fatty acids, i.e., α-linolenic acids (ALA), displays neuroprotective properties. Here, we report the preventive effects of dietary FSO treatment in a rat model of TMT intoxication. The administration of FSO (1 mL/kg, orally) before and over the course of TMT intoxication (a single dose, 8 mg/kg, i.p.) reduced hippocampal cell death, prevented the activation of astrocytes, and inhibited their polarization toward a pro-inflammatory/neurotoxic phenotype. The underlying protective mechanism was delineated through the selective upregulation of BDNF and PI3K/Akt and the suppression of ERK activation in the hippocampus. Pretreatment with FSO reduced cell death and efficiently suppressed the expression of inflammatory molecules. These beneficial effects were accompanied by an increased intrahippocampal content of n-3 fatty acids. In vitro, ALA pretreatment prevented the TMT-induced polarization of cultured astrocytes towards the pro-inflammatory spectrum. Together, these findings support the beneficial neuroprotective properties of FSO/ALA against TMT-induced neurodegeneration and accompanied inflammation and hint at a promising preventive use of FSO in hippocampal degeneration and dysfunction.
摘要：
暴露于神经毒素三甲基锡（TMT）选择性地诱导海马神经元损伤和星形胶质细胞活化，并伴有神经炎症，导致严重的行为，认知，和记忆障碍。大量证据表明，亚麻籽油(FSO)，作为最丰富的必需ω-3脂肪酸来源之一，即，α-亚麻酸（ALA），显示神经保护特性。这里,我们报道了膳食FSO治疗对TMT中毒大鼠模型的预防作用。FSO的给药（1mL/kg，口服)在TMT中毒之前和期间(单剂量，8mg/kg,i.p.）减少海马细胞死亡，防止星形胶质细胞的激活，并抑制它们向促炎/神经毒性表型的极化。通过海马中BDNF和PI3K/Akt的选择性上调和ERK激活的抑制来描述潜在的保护机制。用FSO预处理减少细胞死亡并有效抑制炎症分子的表达。这些有益作用伴随着海马内n-3脂肪酸含量的增加。体外，ALA预处理阻止了TMT诱导的培养星形胶质细胞向促炎光谱的极化。一起,这些发现支持FSO/ALA对TMT诱导的神经变性和伴随的炎症具有有益的神经保护特性,并提示FSO在海马变性和功能障碍中具有良好的预防性应用.
