JNEUROSCI . ORG {
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Title:
Age-Independent Synaptogenesis by Phosphoinositide 3 Kinase | Journal of Neuroscience
Description:
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.
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Keywords {đ}
pik, neurons, scholar, number, synapse, activity, synapses, cell, fig, synaptic, flies, openurlcrossrefpubmedgoogle, control, synaptogenic, signaling, gal, size, akt, full, drosophila, adult, controls, increase, openurlabstractfree, textgoogle, volume, effect, motor, kinase, gsk, growth, brain, larval, inr, insulin, sections, fibers, syngfp, neurosci, overexpression, expression, cells, overexpressing, synaptogenesis, induces, pathway, data, aging, higher, levels,
Topics {âď¸}
tcs-sp2-aobs-uv equipped insulin-induced long-term depression age-related electron-dense bodies development/plasticity/repair age-independent synaptogenesis single-electrode current-clamp rapamycinâphosphatidylinositol 3-kinase-dependent pathway unique synaptotagmin-binding site uasâglycogen synthase kinase phosphoinositide 3-kinase-akt-mammalian target treating sh-sy5y cells synergize β-catenin degradation aberrant beta-catenin signaling crayfish long-term facilitation electron-dense body inclusions genotypes gal4âd42/uasâpi3k92e sh-sy5y cells incubated membrane-bound β-catenin tau-mediated microtubule hyperstability normalized versus β-tubulin ngf-stimulated pc12 cells showing age-characteristic disorganization anti-β-gal antibody uasâpi3k/uasâhrp neurons cd2âfrtâcd8âgfp experience-dependent developmental plasticity bio-rad gs800 densitometer syn-gfp signal drops gal4â796/uasâcd8âgfp custom-built software written ds6k-regulated cell growth gal4âd42/uas-pi3k92e gal4âd42/uasâpi3k92e insulin-mediated pi3k activation full synaptic maturation methods fly strains beta-catenin activity dominant-negative pi3k carrying phosphatidylinositol-3â˛-kinase pathway gal4â796/uasâsyn-gfp pi3k-induced ectopic synapses tyrosine kinase receptors evoke suprathreshold responses gal4âd42/uasâpi3k green fluorescent protein gal4âd42/uasâgsk3 neuron-specific inr knock high-resolution confocal images increases dna synthesis authors editorial board spontaneous neurotransmitter release
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