Martín-Peña Alfonso, Acebes Angel, Rodríguez José-Rodrigo, Sorribes Amanda, de Polavieja Gonzalo G, Fernández-Fúnez Pedro, Ferrús Alberto
Cajal Institute, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
J Neurosci. 2006 Oct 4;26(40):10199-208. doi: 10.1523/JNEUROSCI.1223-06.2006.
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.
突触是神经元之间专门的通讯点，其数量是认知能力的主要决定因素。这些动态结构会经历依赖于发育和活动的变化。在大脑衰老和某些疾病过程中，突触会逐渐丧失，导致智力衰退。因此，确定控制突触数量的分子机制至关重要。我们在此表明，磷脂酰肌醇3激酶（PI3K）的水平在果蝇幼虫运动神经元和成年大脑投射神经元中均调节突触数量。PI3K过表达诱导的多余突触具有功能，并引发行为变化。值得注意的是，PI3K激活也能在老年成年神经元中诱导突触形成。我们证明持续的PI3K活性对于突触维持是必要的。我们还报告称，PI3K控制人类神经母细胞瘤细胞中突触标记物的表达和定位，这表明PI3K的突触生成活性在人类中是保守的。因此，我们提出PI3K刺激可用于预防或延缓正常衰老和神经疾病中的突触丧失。
