Pagliusi S R, Gerrard P, Abdallah M, Talabot D, Catsicas S
Glaxo Institute for Molecular Biology, Geneva, Switzerland.
Neuroscience. 1994 Aug;61(3):429-33. doi: 10.1016/0306-4522(94)90422-7.
Age-related decline of cognition and memory, in humans and other animals, appears to be associated with neuronal loss. Experimental and clinical evidence has shown that the hippocampal formation is one of the brain regions most vulnerable to the ageing process. Because excess of glutamate is neurotoxic to hippocampal neurons, abnormalities in glutamate neurotransmitter function may play a crucial role in neurodegenerative disorders, especially in conjunction with brain ageing. We have used in situ hybridization to study the expression of the two major alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor subunits, involved in the control of calcium permeability in the young adult and aged rat hippocampus. We show that the levels of messenger RNA encoding the AMPA-selective glutamate receptor subunit-1 (GluR1 or GluRA) and AMPA-selective glutamate receptor subunit-2 (GluR2 or GluRB) are highest in the dentate gyrus, followed by the CA1 and CA3 hippocampal subfields. We also show that the levels of both messenger RNAs decrease differentially with age in all subfields of the hippocampus. Finally, the GluR1/GluR2 messenger RNA ratios increase in the aged hippocampus, particularly in the CA3 subfield, suggesting that altered calcium homeostasis may contribute to age-related neuronal death.
在人类和其他动物中，与年龄相关的认知和记忆衰退似乎与神经元丧失有关。实验和临床证据表明，海马结构是大脑中最易受衰老过程影响的区域之一。由于过量的谷氨酸对海马神经元具有神经毒性，谷氨酸神经递质功能异常可能在神经退行性疾病中起关键作用，尤其是与脑老化相关时。我们利用原位杂交技术研究了两种主要的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）选择性谷氨酸受体亚基在年轻成年大鼠和老年大鼠海马体中对钙通透性控制的表达情况。我们发现，编码AMPA选择性谷氨酸受体亚基-1（GluR1或GluRA）和AMPA选择性谷氨酸受体亚基-2（GluR2或GluRB）的信使核糖核酸水平在齿状回中最高，其次是海马体CA1和CA3亚区。我们还发现，在海马体的所有亚区中，这两种信使核糖核酸的水平均随年龄增长而出现不同程度的下降。最后，老年海马体中GluR1/GluR2信使核糖核酸比率升高，尤其是在CA3亚区，这表明钙稳态的改变可能导致与年龄相关的神经元死亡。
