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首页> 外文期刊>The European Journal of Neuroscience >Enrichment enhances the expression of sgk, a glucocorticoid-induced gene, and facilitates spatial learning through glutamate AMPA receptor mediation.
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Enrichment enhances the expression of sgk, a glucocorticoid-induced gene, and facilitates spatial learning through glutamate AMPA receptor mediation.

机译：富集增强了糖皮质激素诱导基因sgk的表达，并通过谷氨酸AMPA受体介导促进了空间学习。

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We have previously demonstrated that the serum and glucocorticoid-inducible kinase (sgk) gene plays a causal role in facilitating memory performance in rats. Environment enrichment is known to facilitate spatial learning. We therefore examined the effect of enrichment on sgk expression. We also examined the role of sgk in spatial and nonspatial learning and the regulation of sgk expression by activation of different glutamate receptors. Both real-time polymerase chain reaction and Western blot analyses revealed that enrichment training preferentially increased sgk mRNA and protein levels in the hippocampus. Transfection of sgk mutant DNA to the hippocampal CA1 area markedly impaired spatial learning, fear-conditioning learning and novel object-recognition learning in rats, but enrichment training effectively reversed these learning deficits. Meanwhile, S422A mutant DNA transfection prevented enrichment-induced spatial learning facilitation. In studying glutamate receptor regulation of sgk expression, we found that blockade of N-methyl-d-aspartate (NMDA) receptors in general, and the NR2B subunit in particular both effectively blocked enrichment-induced spatial learning facilitation, but they did not block enrichment-induced sgk expression. Upon various glutamate agonist infusions, only alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) increased sgk mRNA levels significantly in the hippocampus. Furthermore, blockade of AMPA receptors effectively blocked both enrichment-induced spatial learning facilitation and sgk expression. These results indicate that there is a dissociation between NMDA receptor activation and sgk expression. Enrichment enhanced spatial learning through both NMDA and AMPA receptor activation, whereas enrichment-induced sgk expression is specifically mediated through AMPA receptors. These results suggest that sgk could serve as a novel molecular mechanism, in addition to the NMDA receptor NR2B, underlying enrichment-induced learning facilitation.
机译：我们以前已经证明，血清和糖皮质激素诱导的激酶（sgk）基因在促进大鼠记忆力中起因果作用。众所周知，丰富环境有助于空间学习。因此，我们检查了富集对sgk表达的影响。我们还研究了sgk在空间和非空间学习中的作用以及通过激活不同谷氨酸受体来调节sgk表达的作用。实时聚合酶链反应和蛋白质印迹分析均显示，富集训练优先增加海马中的sgk mRNA和蛋白质水平。 sgk突变体DNA转染海马CA1区显着损害大鼠的空间学习，恐惧条件学习和新颖的对象识别学习，但强化训练有效地逆转了这些学习缺陷。同时，S422A突变体DNA转染阻止了富集诱导的空间学习促进。在研究谷氨酸受体对sgk表达的调节中，我们发现一般而言N-甲基-d-天冬氨酸（NMDA）受体的阻滞，尤其是NR2B亚基均能有效阻滞富集诱导的空间学习促进，但它们并未阻止富集-诱导的sgk表达。各种谷氨酸激动剂输注后，仅α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）在海马中显着增加了sgk mRNA水平。此外，对AMPA受体的阻断有效地阻断了富集诱导的空间学习促进和sgk表达。这些结果表明，NMDA受体激活与sgk表达之间存在解离。富集通过NMDA和AMPA受体激活增强了空间学习，而富集诱导的sgk表达是通过AMPA受体特异性介导的。这些结果表明，sgk可以作为一种新的分子机制，除了NMDA受体NR2B以外，还可能是致富诱导学习的基础。

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