title: Age-independent synaptogenesis by phosphoinositide 3 kinase.
abstract: Synapses are specialized communication points between neurons, and their number is a major determinant of cognitive abilities. These dynamic structures undergo developmental- and activity-dependent changes. During brain aging and certain diseases, synapses are gradually lost, causing mental decline. It is, thus, critical to identify the molecular mechanisms controlling synapse number. We show here that the levels of phosphoinositide 3 kinase (PI3K) regulate synapse number in both Drosophila larval motor neurons and adult brain projection neurons. The supernumerary synapses induced by PI3K overexpression are functional and elicit changes in behavior. Remarkably, PI3K activation induces synaptogenesis in aged adult neurons as well. We demonstrate that persistent PI3K activity is necessary for synapse maintenance. We also report that PI3K controls the expression and localization of synaptic markers in human neuroblastoma cells, suggesting that PI3K synaptogenic activity is conserved in humans. Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders.
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martín-Peña
authors.forename: Angel
authors.initials: A
authors.lastname: Acebes
authors.forename: José-Rodrigo
authors.initials: JR
authors.lastname: Rodríguez
authors.forename: Amanda
authors.initials: A
authors.lastname: Sorribes
authors.forename: Gonzalo G
authors.initials: GG
authors.lastname: de Polavieja
authors.forename: Pedro
authors.initials: P
authors.lastname: Fernández-Fúnez
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferrús
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D009046:Motor Neurons / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology*
chemical_list: D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases