Pandey Surya P, Rai Rakesh, Gaur Pankaj, Prasad S
Biochemistry and Molecular Biology Laboratory, Department of Zoology, Brain Research Centre, Banaras Hindu University, Varanasi, 221005, India.
Biogerontology. 2015 Jun;16(3):317-28. doi: 10.1007/s10522-014-9548-6. Epub 2015 Jan 6.
AMPA type glutamate receptor (AMPAR) on the post synaptic membrane plays important role in the process of synaptic plasticity involving various scaffolding and trafficking proteins. However, their alterations during development- and aging are not well understood. Here, we report that the expression of AMPAR-GluR2 subunit is gradually up regulated in the hippocampus from 0 day to adult (20 week) and down regulated thereafter in 70 week old male mice. This pattern of GluR2 during development (0-, 7- and 15 day), maturation (45 day) and adult age resembles with similar expression pattern of the scaffolding protein PSD95. Expression pattern of Stargazin (TARPγ-2) largely follows almost similar pattern up to adult age but is up regulated in old age. Pattern of PICK1 expression, however, is opposite to our GluR2 data till adult age but its expression is significantly down regulated in old age. Our data on alterations in the expression of GluR2 in the hippocampus during development and aging indicates a high- and low positive correlations with PSD95 and Stargazin, respectively whereas negative correlation with PICK1 except in old age where expression of Stargazin is higher and that of PICK1 is lower. Our findings suggest that increasing expression pattern of GluR2 during developmental periods and at adult age may be associated with achieving cognitive abilities whereas its low expression in old age may be linked with cognitive decline and proteins like PSD95, Stargazin and PICK1 might be differentially associated with development- and age-dependent alterations in AMPAR-dependent synaptic plasticity and hence learning and memory.
突触后膜上的AMPA型谷氨酸受体(AMPAR)在涉及各种支架蛋白和转运蛋白的突触可塑性过程中发挥着重要作用。然而,它们在发育和衰老过程中的变化尚未得到充分了解。在此,我们报告,在雄性小鼠中,AMPAR-GluR2亚基的表达在海马体中从0天到成年(20周)逐渐上调,此后在70周龄时下调。GluR2在发育阶段(0天、7天和15天)、成熟阶段(45天)和成年期的这种表达模式与支架蛋白PSD95的相似表达模式相似。Stargazin(TARPγ-2)的表达模式在成年之前基本遵循几乎相似的模式,但在老年时上调。然而,PICK1的表达模式在成年之前与我们的GluR2数据相反,但其表达在老年时显著下调。我们关于海马体中GluR2在发育和衰老过程中表达变化的数据表明,它与PSD95和Stargazin分别呈高正相关和低正相关,而与PICK1呈负相关,但在老年时Stargazin表达较高而PICK1表达较低。我们的研究结果表明,GluR2在发育阶段和成年期表达模式的增加可能与认知能力的获得有关,而其在老年时的低表达可能与认知衰退有关,并且PSD95、Stargazin和PICK1等蛋白质可能与依赖AMPAR的突触可塑性以及学习和记忆中的发育和年龄依赖性变化存在差异关联。