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首页> 外文期刊>Journal of neuroendocrinology >Decreased Npas4 and Arc mRNA Levels in the Hippocampus of Aged Memory-Impaired Wild-Type But Not Memory Preserved 11 beta-HSD1 Deficient Mice
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Decreased Npas4 and Arc mRNA Levels in the Hippocampus of Aged Memory-Impaired Wild-Type But Not Memory Preserved 11 beta-HSD1 Deficient Mice

机译:老年记忆障碍的野生型但不是记忆保存的11β-HSD1缺陷小鼠海马中的Npas4和Arc mRNA水平降低

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Mice deficient in the glucocorticoid-regenerating enzyme 11 beta-HSD1 resist age-related spatial memory impairment. To investigate the mechanisms and pathways involved, we used microarrays to identify differentially expressed hippocampal genes that associate with cognitive ageing and 11b-HSD1. Aged wild-type mice were separated into memory-impaired and unimpaired relative to young controls according to their performance in the Y-maze. All individual aged 11 beta-HSD1-deficient mice showed intact spatial memory. The majority of differentially expressed hippocampal genes were increased with ageing (e.g. immune/inflammatory response genes) with no genotype differences. However, the neuronal-specific transcription factor, Npas4, and immediate early gene, Arc, were reduced (relative to young) in the hippocampus of memory-impaired but not unimpaired aged wild-type or aged 11b-HSD1-deficient mice. A quantitative reverse transcriptase-polymerase chain reaction and in situ hybridisation confirmed reduced Npas4 and Arc mRNA expression in memory-impaired aged wild-type mice. These findings suggest that 11 beta-HSD1 may contribute to the decline in Npas4 and Arc mRNA levels associated with memory impairment during ageing, and that decreased activity of synaptic plasticity pathways involving Npas4 and Arc may, in part, underlie the memory deficits seen in cognitively-impaired aged wild-type mice.
机译:缺乏糖皮质激素再生酶11βHSD1的小鼠抵抗与年龄有关的空间记忆障碍。为了研究涉及的机制和途径,我们使用微阵列识别与认知衰老和11b-HSD1相关的差异表达的海马基因。根据年幼的野生型小鼠在Y型迷宫中的表现,将它们分为记忆受损和未受损的幼鼠。所有个体衰老的11个beta-HSD1缺陷小鼠均显示完整的空间记忆。大多数差异表达的海马基因随着衰老而增加(例如免疫/炎症反应基因),而没有基因型差异。但是,神经元特异性转录因子Npas4和立即早期基因Arc在记忆受损但未受损的野生型或老年11b-HSD1缺陷小鼠的海马中减少(相对于年轻)。定量逆转录酶-聚合酶链反应和原位杂交证实,记忆力减退的老年野生型小鼠中Npas4和Arc mRNA表达降低。这些发现表明,11β-HSD1可能会导致衰老过程中与记忆障碍相关的Npas4和Arc mRNA水平下降,并且涉及Npas4和Arc的突触可塑性通路活性降低可能部分是由于认知障碍所致受损的老年野生型小鼠。

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