Nutrition is a crucial component for maintenance of brain function and mental health. Accumulating evidence suggests that certain molecular compounds derived from diet can exert neuroprotective effects against chronic stress, and moreover improve important neuronal processes vulnerable to the stress response, such as plasticity and neurogenesis. Phospholipids are naturally occurring amphipathic molecules with promising potential to promote brain health. However, it is unclear whether phospholipids are able to modulate neuronal function directly under a stress-related context. In this study, we investigate the neuroprotective effects of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), sphingomyelin (SM) and cardiolipin (CL) against corticosterone (CORT)-induced cytotoxicity in primary cultured rat cortical neurons. In addition, we examine their capacity to modulate proliferation and differentiation of hippocampal neural progenitor cells (NPCs).

We show that PS, PG and PE can reverse CORT-induced cytotoxicity and neuronal depletion in cortical cells. On the other hand, phospholipid exposure was unable to prevent the decrease of Bdnf expression produced by CORT. Interestingly, PS was able to increase hippocampal NPCs neurosphere size, and PE elicited a significant increase in astrocytic differentiation in hippocampal NPCs. Together, these results indicate that specific phospholipids protect cortical cells against CORT-induced cytotoxicity and improve proliferation and astrocytic differentiation in hippocampal NPCs, suggesting potential implications on neurodevelopmental and neuroprotective pathways relevant for stress-related disorders.

营养是维持脑功能和心理健康的重要组成部分。越来越多的证据表明，某些源自饮食的分子化合物可以对慢性应激产生神经保护作用，而且可以改善易受应激反应影响的重要神经元过程，例如可塑性和神经发生。磷脂是天然存在的两亲分子，具有促进大脑健康的潜力。然而，尚不清楚磷脂是否能够在压力相关的情况下直接调节神经元功能。在这项研究中，我们研究了磷脂酰胆碱（PC），溶血磷脂酰胆碱（LPC），磷脂酰丝氨酸（PS），磷脂酰乙醇胺（PE），磷脂酰肌醇（PI），磷脂酰甘油（PG），磷脂酸（PA），鞘磷脂（SM）和心磷脂（CL）对抗皮质酮（CORT）诱导的原代培养大鼠皮质神经元的细胞毒性。此外，我们检查了它们调节海马神经祖细胞（NPC）增殖和分化的能力。

我们显示PS，PG和PE可以逆转CORT诱导的皮质细胞毒性和神经元耗竭。另一方面，磷脂暴露不能防止CORT产生的Bdnf表达下降。有趣的是，PS能够增加海马NPC的神经球大小，而PE引起海马NPC的星形细胞分化显着增加。总之，这些结果表明，特定的磷脂可以保护皮质细胞免受CORT诱导的细胞毒性，并改善海马NPC中的增殖和星形胶质细胞分化，表明对与压力相关疾病相关的神经发育和神经保护途径可能产生影响。