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Strain-dependent hippocampal protein levels of GABA(B)-receptor subunit 2 and NMDA-receptor subunit 1.

机译:GABA(B)受体亚基2和NMDA受体亚基1的应变依赖性海马蛋白水平。

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摘要

Mouse strains differ from one another in cognitive function as learning and memory as well as synaptic plasticity. Although molecular explanations for this heterogeneity have been proposed, there is no available information on strain-dependent GABA(B)-receptor levels in hippocampus that may explain observed differences in GABA(B)-receptor-mediated cognitive enhancement among strains. This formed the rationale to perform a study on GABA(B) and related somatostatin receptor 5 and NMDA receptors that have been reported to be involved in memory enhancement by GABA(B)-antagonism. Hippocampi of three inbred (C57BL/6J, DBA/2, BalbC) and three outbred (OF1, CD1, CF1) mouse strains were taken. Membrane fractions were prepared and subsequently levels of GABA(B)-receptor subunits 1 and 2, NMDA-receptor subunits 1 and 2a and b, as well as somatostatin receptor 5 were determined by immunoblotting. NMDA-receptor subunit 1 levels were significantly higher in C57BL/6J than in DBA/2. GABA(B)-receptor subunit 2 levels were significantly decreased in C57BL/6J as compared to OF1, CD1, CF1 and DBA/2. No statistically significant differences for other receptors were observed. Different NMDA-receptor subunit 1 and GABA(B)-receptor subunit 2 levels observed in naive mouse strains reflect strain-dependent expression of subunits and are proposed to lead to altered stoichiometry of GABA(B)-receptor complexes. Modification of receptor complex stoichiometry in the hippocampus in turn may well be responsible for cognitive differences observed in spatial memory between mouse strains.
机译:小鼠品系在认知功能(如学习和记忆)以及突触可塑性方面彼此不同。尽管已提出了对此异质性的分子解释,但尚无关于海马中应变依赖型GABA(B)-受体水平的可用信息,这可能解释了所观察到的菌株之间GABA(B)-受体介导的认知增强的差异。这形成了对GABA(B)和相关生长抑素受体5和NMDA受体进行研究的基本原理,据报道这些生长激素抑制素受体5和NMDA受体与GABA(B)拮抗作用有关。取了三个自交系(C57BL / 6J,DBA / 2,BalbC)和三个外交系(OF1,CD1,CF1)小鼠海马。制备膜级分,随后通过免疫印迹测定GABA(B)-受体亚基1和2,NMDA-受体亚基1和2a和b以及生长抑素受体5的水平。 C57BL / 6J中的NMDA受体亚基1水平显着高于DBA / 2。与OF1,CD1,CF1和DBA / 2相比,C57BL / 6J中的GABA(B)-受体亚基2水平显着降低。没有观察到其他受体的统计学显着差异。天真小鼠品系中观察到的不同NMDA受体亚基1和GABA(B)-受体亚基2的水平反映了亚基的依赖于应变的表达,并被提议导致GABA(B)-受体复合物化学计量的改变。反过来,海马受体复合物化学计量的改变很可能是小鼠品系之间在空间记忆中观察到的认知差异的原因。

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