title: Phosphoinositide-3-kinase activation controls synaptogenesis and spinogenesis in hippocampal neurons.
abstract: The possibility of changing the number of synapses may be an important asset in the treatment of neurological diseases. In this context, the synaptogenic role of the phosphoinositide-3-kinase (PI3K) signaling cascade has been previously demonstrated in Drosophila. This study shows that treatment with a PI3K-activating transduction peptide is able to promote synaptogenesis and spinogenesis in primary cultures of rat hippocampal neurons, as well as in CA1 hippocampal neurons in vivo. In culture, the peptide increases synapse density independently of cell density, culture age, dendritic complexity, or synapse type. The induced synapses also increase neurotransmitter release from cultured neurons. The synaptogenic signaling pathway includes PI3K-Akt. Furthermore, the treatment is effective on adult neurons, where it induces spinogenesis and enhances the cognitive behavior of treated animals in a fear-conditioning assay. These findings demonstrate that functional synaptogenesis can be induced in mature mammalian brains through PI3K activation.
authors.affiliation: Structural Synaptic Plasticity Lab, Department of Neurodegenerative Diseases, Centro de Investigación Biomédica de la Rioja, La Rioja 26006, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Cuesto
authors.forename: Lilian
authors.initials: L
authors.lastname: Enriquez-Barreto
authors.forename: Cristina
authors.initials: C
authors.lastname: Caramés
authors.forename: Marta
authors.initials: M
authors.lastname: Cantarero
authors.forename: Xavier
authors.initials: X
authors.lastname: Gasull
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferrús
authors.forename: Ángel
authors.initials: Á
authors.lastname: Acebes
authors.forename: Miguel
authors.initials: M
authors.lastname: Morales
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000201:enzymology* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000201:enzymology* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000201:enzymology* / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases