α‐Glyceryl‐phosphoryl‐ethanolamine protects human hippocampal neurons from ageing‐induced cellular alterations

Abstract

Brain ageing has been related to a decrease in cellular metabolism, to an accumulation of misfolded proteins and to an alteration of the lipid membrane composition. These alterations act as contributive aspects of age‐related memory decline by reducing membrane excitability and neurotransmitter release. In this sense, precursors of phospholipids (PLs) can restore the physiological composition of cellular membranes and ameliorate the cellular defects associated with brain ageing. In particular, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) have been shown to restore mitochondrial function, reduce the accumulation of amyloid beta (Aβ) and, at the same time, provide the amount of acetylcholine needed to reduce memory deficit. Among PL precursors, alpha‐glycerylphosphorylethanolamine (GPE) has shown to protect astrocytes from Aβ injuries and to slow‐down ageing of human neural stem cells. GPE has been evaluated in aged human hippocampal neurons, which are implicated in learning and memory, and constitute a good in vitro model to investigate the beneficial properties of GPE. In order to mimic cellular ageing, the cells have been maintained 21 days in vitro and challenged with GPE. Results of the present paper showed GPE ability to increase PE and PC content, glucose uptake and the activity of the chain respiratory complex I and of the GSK‐3β pathway. Moreover, the nootropic compound showed an increase in the transcriptional/protein levels of neurotrophic and well‐being related genes. Finally, GPE counteracted the accumulation of ageing‐related misfolded proteins (a‐synuclein and tau). Overall, our data underline promising effects of GPE in counteracting cellular alterations related to brain ageing and cognitive decline.