Abstract
Brain aging involves changes in the lipid membrane composition that lead to a decrease in membrane excitability and neurotransmitter release. These membrane modifications have been identified as contributing factors in age-related memory decline. In this sense, precursors of phospholipids (PLs) can restore the physiological composition of cellular membranes and produce valuable therapeutic effects in brain aging. Among promising drugs, alpha-glycerylphosphorylethanolamine (GPE) has demonstrated protective effects in amyloid-injured astrocytes and in an aging model of human neural stem cells. However, the compound properties on mature neuronal cells remain unexplored. Herein, GPE was tested in human hippocampal neurons, which are involved in learning and memory, and characterized by a functional cholinergic transmission, thus representing a valuable cellular model to explore the beneficial properties of GPE. GPE induced the release of the main membrane phospholipids and of the acetylcholine neurotransmitter. Moreover, the compound reduced lipid peroxidation and enhanced membrane fluidity of human brain cells. GPE counteracted the DNA damage and viability decrease observed in in vitro aged neurons. Among GPE treatment effects, the autophagy was found positively upregulated. Overall, these results confirm the beneficial effects of GPE treatment and suggest the compound as a promising drug to preserve hippocampal neurons and virtually memory performances.
Highlights
Brain aging has been related to peculiar structural and functional alterations that include neuronal and astrocyte degeneration, neuroinflammation and changes in the plasma membrane composition [1,2,3]
GPE was tested in human hippocampal neurons, which are involved in learning and memory, and characterized by a functional cholinergic transmission, representing a valuable cellular model to explore the beneficial properties of GPE
Such alterations lead to a decrease in membrane fluidity and cholinergic activities, which depend on phosphatidylcholine (PC) and PUFAs for excitability and neurotransmitter release, via retarded Na+/Ca+ channels [4,5]
Summary
Brain aging has been related to peculiar structural and functional alterations that include neuronal and astrocyte degeneration, neuroinflammation and changes in the plasma membrane composition [1,2,3]. Since PLs can promote PUFA transport, external PLs can restore the physiological composition of brain cellular membranes and produce valuable therapeutic effects in brain aging [4,5,11,12] In this respect, explicit memory has been demonstrated to be enhanced by phosphatidylcholine (PC) administration via the release of choline [1,13] which is a constituent of the cellular membrane and an acetylcholine (Ach) precursor [1]. The aim of the present study was to investigate GPE effects on human hippocampal neurons These cells have been widely demonstrated to have functional cholinergic transmission [18] and play a pivotal role in cognition, learning and memory [19], representing a valuable cellular model to explore GPE neuroprotective properties
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