Group 1 metabotropic glutamate receptor function and its regulation of learning and memory in the aging brain.
Group 1 metabotropic glutamate receptor function and its regulation of learning and memory in the aging brain.
复制标题
DOI：
10.3389/fphar.2012.00182
复制
发表时间：
2012
影响因子：
5.6
通讯作者：
Quirion R
中科院分区：
文献类型：
--
作者：
Ménard C;Quirion R
正常衰老的一般特征是认知能力缓慢下降，尽管个体差异显著。已经研究了几种动物模型来探索这种现象背后的分子和细胞机制。兴奋性神经递质谷氨酸及其受体与空间学习和海马依赖性记忆过程密切相关。几十年来，已知离子型谷氨酸受体在突触可塑性中起关键作用，突触可塑性是调节记忆形成的一种适应形式。在过去的10年里，一些研究小组已经证明了第1组代谢型谷氨酸受体（mGluR）在成功的认知衰老中的重要性。这些G蛋白偶联受体在海马结构中富集，并与膜中的其他蛋白质（包括谷氨酸离子型受体）发生物理相互作用。突触可塑性对于维持认知能力和由第1组mGluR激活诱导的长期抑郁（LTD）至关重要，这与衰老大脑中的记忆有关。通过mGluR-LTD的蛋白质翻译和合成调节离子型受体运输和与认知相关的立即早期基因的表达。脆性X综合征是一种以记忆缺陷为特征的自闭症遗传形式，与mGluR受体功能障碍及其下游信号通路的异常激活有关。mGluR功能障碍也可能与阿尔茨海默病（AD）等神经退行性疾病有关。事实上，β-淀粉样蛋白，不溶性老年斑的主要成分和AD的标志之一，阻塞mGluR依赖性LTD，导致功能性突触减少。这篇综述强调了最近的研究结果，mGluR信号，相关的突触可塑性，以及它们在正常衰老和神经系统疾病的潜在参与。
Normal aging is generally characterized by a slow decline of cognitive abilities albeit with marked individual differences. Several animal models have been studied to explore the molecular and cellular mechanisms underlying this phenomenon. The excitatory neurotransmitter glutamate and its receptors have been closely linked to spatial learning and hippocampus-dependent memory processes. For decades, ionotropic glutamate receptors have been known to play a critical role in synaptic plasticity, a form of adaptation regulating memory formation. Over the past 10 years, several groups have shown the importance of group 1 metabotropic glutamate receptor (mGluR) in successful cognitive aging. These G-protein-coupled receptors are enriched in the hippocampal formation and interact physically with other proteins in the membrane including glutamate ionotropic receptors. Synaptic plasticity is crucial to maintain cognitive abilities and long-term depression (LTD) induced by group 1 mGluR activation, which has been linked to memory in the aging brain. The translation and synthesis of proteins by mGluR-LTD modulate ionotropic receptor trafficking and expression of immediate early genes related to cognition. Fragile X syndrome, a genetic form of autism characterized by memory deficits, has been associated to mGluR receptor malfunction and aberrant activation of its downstream signaling pathways. Dysfunction of mGluR could also be involved in neurodegenerative disorders like Alzheimer’s disease (AD). Indeed, beta-amyloid, the main component of insoluble senile plaques and one of the hallmarks of AD, occludes mGluR-dependent LTD leading to diminished functional synapses. This review highlights recent findings regarding mGluR signaling, related synaptic plasticity, and their potential involvement in normal aging and neurological disorders.
登录
查看更多内容
影响因子：
3.6
作者：
Auclair, Agnes L.;Besnard, Joel;Depoortere, Ronan
通讯作者：
Depoortere, Ronan
影响因子：
2.5
作者：
Auerbach, Benjamin D.;Bear, Mark F.
通讯作者：
Bear, Mark F.
影响因子：
3.5
作者：
Ango, F;Robbe, D;Fagni, L
通讯作者：
Fagni, L
影响因子：
4.7
作者：
Bortolotto, ZA;Collett, VJ;Collingridge, GL
通讯作者：
Collingridge, GL
DOI：
10.1523/jneurosci.2036-08.2008
发表时间：
2008-08-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Boric K;Muñoz P;Gallagher M;Kirkwood A
通讯作者：
Kirkwood A