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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >11beta-hydroxysteroid dehydrogenase type 1 expression is increased in the aged mouse hippocampus and parietal cortex and causes memory impairments.
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11beta-hydroxysteroid dehydrogenase type 1 expression is increased in the aged mouse hippocampus and parietal cortex and causes memory impairments.

机译:11β-羟类固醇脱氢酶1型表达在老年小鼠海马和顶叶皮层中增加,并引起记忆障碍。

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摘要

Increased neuronal glucocorticoid exposure may underlie interindividual variation in cognitive function with aging in rodents and humans. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the regeneration of active glucocorticoids within cells (in brain and other tissues), thus amplifying steroid action. We examined whether 11beta-HSD1 plays a role in the pathogenesis of cognitive deficits associated with aging in male C57BL/6J mice. We show that 11beta-HSD1 levels increase with age in CA3 hippocampus and parietal cortex, correlating with impaired cognitive performance in the water maze. In contrast, neither circulating corticosterone levels nor tissue corticosteroid receptor expression correlates with cognition. 11beta-HSD1 elevation appears causal, since aging (18 months) male transgenic mice with forebrain-specific 11beta-HSD1 overexpression ( approximately 50% in hippocampus) exhibit premature age-associated cognitive decline in the absence of altered circulating glucocorticoid levels or other behavioral (affective) deficits. Thus, excess 11beta-HSD1 in forebrain is a cause of as well as a therapeutic target in memory impairments with aging.
机译:在啮齿动物和人类中,随着年龄的增长,神经元糖皮质激素暴露的增加可能是个体间认知功能变化的基础。 11β-羟基类固醇脱氢酶1(11beta-HSD1)催化细胞(大脑和其他组织)中活性糖皮质激素的再生,从而增强了类固醇的作用。我们检查了11beta-HSD1是否在与雄性C57BL / 6J小鼠衰老相关的认知缺陷的发病机理中起作用。我们显示,CA3海马和顶叶皮层中11beta-HSD1水平随年龄增加而增加,与水迷宫中认知能力受损有关。相反,循环皮质酮水平或组织糖皮质激素受体表达均与认知无关。 11beta-HSD1升高似乎是有原因的,因为在没有改变的糖皮质激素水平或其他行为改变的情况下,具有前脑特异性11beta-HSD1过表达的雄性转基因小鼠(约18%)(在海马中约占50%)表现出与年龄相关的早衰。情感缺陷)。因此,前脑中过量的11beta-HSD1是衰老导致记忆障碍的原因和治疗目标。

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