Neurobiological effects of phospholipids in vitro: Relevance to stress-related disorders

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.