Changes in molecular composition of rat medial prefrontal cortex synapses during adolescent development
Changes in molecular composition of rat medial prefrontal cortex synapses during adolescent development
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DOI：
10.1111/j.1460-9568.2010.07404.x
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发表时间：
2010-11-01
影响因子：
3.4
通讯作者：
Spijker, Sabine
中科院分区：
文献类型：
--
作者：
Counotte, Danielle S.;Li, Ka Wan;Spijker, Sabine
出生后的大脑发育在整个青春期持续到成年早期。特别是，突触加强和消除是青春期的突出过程。然而，这个相对较晚的突触发育阶段的分子数据是稀疏的。在这项研究中，我们使用iTRAQ（isobaric标签的相对和绝对定量）为基础的蛋白质组学和电子显微镜研究的突触膜组分从青少年出生后第34天（P）和P44和成年（P78）大鼠内侧前额叶皮层的分子组成。蛋白质的差异表达在青春期早期和青年期之间最为突出（35%，P34-P78），在青春期发育期间（P34和P44之间）细胞膜蛋白过度表达，在青春期晚期和青年期之间（P44-P78）突触囊泡蛋白过度表达。表明发育的关键时期，我们发现，在P34和P44之间，大量的蛋白质差异表达（14%），远远超过青春期后的时期，即P44和P78之间（5%）。一个引人注目的观察是发育的非化学计量调节不同类别的蛋白质从突触囊泡和突触前释放机制。电子显微镜显示P34和P44之间停靠囊泡的数量有微小变化，但突触囊泡的总数和囊泡簇的大小没有变化。我们的结论是，突触的分子组成，更具体地说，突触释放机制，内侧前额叶皮层的变化在青少年的发展急剧。
Postnatal brain development continues throughout adolescence into young adulthood. In particular, synapse strengthening and elimination are prominent processes during adolescence. However, molecular data of this relatively late stage of synaptic development are sparse. In this study, we used iTRAQ (isobaric tag for relative and absolute quantification)-based proteomics and electron microscopy to investigate the molecular composition of a synaptic membrane fraction from adolescent postnatal day (P)34 and P44 and adult (P78) rat medial prefrontal cortex. Differential expression of proteins was most prominent between early adolescence and young adulthood (35%, P34-P78), with an over-representation of cell-membrane proteins during adolescent development (between P34 and P44), and synaptic vesicle proteins between late adolescence and young adulthood (P44-P78). Indicative of the critical period of development, we found that, between P34 and P44, a substantial number of proteins was differentially expressed (14%), much more than during the period after adolescence, i.e. between P44 and P78 (5%). A striking observation was the developmental non-stoichiometric regulation of distinct classes of proteins from the synaptic vesicle and the presynaptic release machinery. Electron microscopy demonstrated a small change in the number of docked vesicles between P34 and P44, but not in the total number of synaptic vesicles and in the size of the vesicle cluster. We conclude that the molecular composition of synapses, and more specifically the synaptic release machinery, of the medial prefrontal cortex changes drastically during adolescent development.