title: Human Neural Stem Cell Aging Is Counteracted by α-Glycerylphosphorylethanolamine.
abstract: Neural stem cells (NSCs) represent a subpopulation of cells, located in specific regions of the adult mammalian brain, with the ability of self-renewing and generating neurons and glia. In aged NSCs, modifications in the amount and composition of membrane proteins/lipids, which lead to a reduction in membrane fluidity and cholinergic activities, have been reported. In this respect, molecules that are effective at normalizing the membrane composition and cholinergic signaling could counteract stem cell aging. α-Glycerylphosphorylethanolamine (GPE), a nootropic drug, plays a role in phospholipid biosynthesis and acetylcholine release. Herein, GPE was assayed on human NSC cultures and on hydroxyurea-aged cells. Using cell counting, colorimetric, and fluorimetric analyses, immunoenzymatic assays, and real time PCR experiments, NSC culture proliferation, senescence, reactive oxygen species, and ADP/ATP levels were assessed. Aged NSCs exhibited cellular senescence, decreased proliferation, and an impairment in mitochondrial metabolism. These changes included a substantial induction in the nuclear factor NF-κB, a key inflammatory mediator. GPE cell treatment significantly protected the redox state and functional integrity of mitochondria, and counteracted senescence and NF-κB activation. In conclusion, our data show the beneficial properties of GPE in this model of stem cell aging.
authors.affiliation: Department of Pharmacy, University of Pisa , Pisa 56126, Italy.|Department of Pharmacological and Biomolecular Sciences, University of Milan , 20122 Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Daniele
authors.affiliation: Department of Pharmacy, University of Pisa , Pisa 56126, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Da Pozzo
authors.affiliation: Department of Pharmacy, University of Pisa , Pisa 56126, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Iofrida
authors.affiliation: Department of Pharmacy, University of Pisa , Pisa 56126, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D017304:Annexin A5; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C002449:glycerophosphoethanolamine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002794:Choline; D000109:Acetylcholine; D006918:Hydroxyurea
keywords: aging; cellular membrane; inflammation; neural stem cell; oxidative stress; phospholipid precursor; α-Glycerylphosphorylethanolamine