Plasticity-related regulation of the hippocampal proteome
Plasticity-related regulation of the hippocampal proteome
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DOI：
10.1111/j.1460-9568.2005.04542.x
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发表时间：
2006-01-01
影响因子：
3.4
通讯作者：
Cobb, SR
中科院分区：
文献类型：
--
作者：
McNair, K;Davies, CH;Cobb, SR
突触可塑性被认为是中枢神经系统重构其神经回路能力的关键机制。大量的研究集中在研究单个蛋白质、生化途径和结构过程如何改变突触可塑性的诱导和维持。然而，突触可塑性可能涉及激活的神经回路内的多个蛋白质复合物的时间和空间协调调节。通过使用全球蛋白质组学为基础的方法，我们现在已经能够揭示，高度多样化的蛋白质类表现出改变表达的谷氨酸受体的激活和诱导的海马体中的谷氨酸能突触强度的长时程增强（LTP）;一个大脑区域，其中塑性突触修饰被认为是认知过程的关键，如空间学习。在本研究中检测到的2946个可分辨的蛋白质点中，79个（2.7%）在响应于100 μ M谷氨酸的施用时在丰度上显著改变（所有P < 0.05）。这些变化中的大多数（56/79）是由于谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型的激活。同样，LTP的诱导与2.4%的可检测的蛋白质组在早期（10分钟）阶段和1.7%在其发展的晚期（4小时）阶段的丰度改变。所观察到的时间和蛋白质类特异性表达模式的变化描绘了广泛的转变，从代谢到结构蛋白质的改变作为可塑性过程的成熟。
Plasticity of glutamatergic synapses is considered to be a pivotal mechanism underlying the ability of the CNS to reconfigure its neural circuits. A large number of studies have focused on investigating how individual proteins, biochemical pathways and structural processes alter both the induction and maintenance of synaptic plasticity. However, it is likely that synaptic plasticity involves temporally and spatially coordinated regulation of multiple protein complexes within the activated neural circuit. By using a global proteomics-based approach we have now been able to reveal that highly diverse protein classes exhibit altered expression in response to both the activation of glutamate receptors and the induction of long-term potentiation (LTP) of glutamatergic synaptic strength in the hippocampus; a brain area where plastic synaptic modification is believed to be key to cognitive processes, such as spatial learning. Of the 2946 resolvable protein spots detected in this study, 79 (2.7%) were significantly altered in abundance in response to 100 mu M glutamate application (all P < 0.05). The majority (56 out of 79) of these changes were due to the activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Likewise, the induction of LTP was associated with an altered abundance of 2.4% of the detectable proteome during the early (10 min) phase and 1.7% during the late (4 h) phase of its development. Observed changes in temporal and protein class-specific patterns of expression depict a widespread shift from metabolic to structural protein alteration as the plasticity process matures.