Aging and surface expression of hippocampal NMDA receptors
Aging and surface expression of hippocampal NMDA receptors
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DOI：
10.1074/jbc.c200074200
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发表时间：
2002-04-26
影响因子：
4.8
通讯作者：
Browning, MD
中科院分区：
文献类型：
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作者：
Clayton, DA;Grosshans, DR;Browning, MD
众所周知，衰老会改变大脑中的许多生理过程，包括突触反应、长期增强、学习和记忆。衰老也被证明会改变n -甲基- d -天冬氨酸（NMDA）受体在许多不同大脑区域的表达和分布，包括海马。此外，我们最近报道了年轻成年大鼠在NMDA受体的表面表达中表现出活性依赖性的增加。我们在老年动物的研究中扩展了这些观察结果，发现老年Fischer 344大鼠在NMDA受体的表面分布上没有表现出活动依赖性的变化。结合这一观察，我们还注意到老年大鼠在NR1亚基的C2剪接变体中表现出表达缺陷。这个亚基在年轻的成年动物受到刺激后优先转移到表面。由于NMDA受体被认为在神经元信号传导中起着重要作用，这些观察结果表明，该受体可能存在新的功能障碍，这可能是神经元生理学中与年龄相关的缺陷的基础。
Aging is known to alter many physiological processes within the brain including synaptic responses, long-term potentiation, learning, and memory. Aging has also been shown to alter the expression and distribution of N-methyl-D-aspartate (NMDA) receptors in many different brain regions, including the hippocampus. Additionally, we have recently reported that young adult rats show an activity-dependent increase in the surface expression of NMDA receptors. We have extended these observations in the present study in aged animals and have found that aged Fischer 344 rats fail to show activity-dependent changes in the surface distribution of NMDA receptors. In conjunction with this observation we have also noted that aged rats show an expression deficit in the C2 splice variant of the NR1 subunit. This subunit is preferentially shifted to the surface following stimulation in young adult animals. As the NMDA receptor is thought to play an important role in neuronal signaling, these observations suggest possible new areas of dysfunction in this receptor that might underlie age-related deficits in neuronal physiology.