动物实验提示：糖皮质激素水平过高有损记忆
Stress hormone impacts memory, learning in diabetic rodentsPublic release date: 17-Feb-2008
Diabetes is known to impair the cognitive health of people, but now scientists have identified one potential mechanism underlying these learning and memory problems. A new National Institutes of Health (NIH) study in diabetic rodents finds that increased levels of a stress hormone produced by the adrenal gland disrupt the healthy functioning of the hippocampus, the region of the brain responsible for learning and short-term memory. Moreover, when levels of the adrenal glucocorticoid hormone corticosterone (also known as cortisol in humans) are returned to normal, the hippocampus recovers its ability to build new cells and regains the “plasticity” needed to compensate for injury and disease and adjust to change.
The study appears in the Feb. 17, 2008, issue of Nature Neuroscience and was conducted by the National Institute on Aging (NIA), part of the NIH. NIA’s Mark Mattson, Ph.D., and colleagues in the Institute’s Intramural Research Program performed the study with Alexis M. Stranahan, a graduate student at Princeton University in New Jersey.
“This research in animal models is intriguing, suggesting the possibility of novel approaches in preventing and treating cognitive impairment by maintaining normal levels of glucocorticoid,” said Richard J. Hodes, M.D., NIA director. “Further study will provide a better understanding of the often complex interplay between the nervous system, hormones and cognitive health.”
Cortisol production is controlled by the hypothalamic-pituitary axis (HPA), a hormone-producing system involving the hypothalamus and pituitary gland in the brain and the adrenal gland located near the kidney. People with poorly controlled diabetes often have an overactive HPA axis and excessive cortisol produced by the adrenal gland. To study the interaction between elevated stress hormones and the hippocampal function, researchers tested the cognitive abilities and examined the brain tissue in animal models of rats with Type 1 diabetes (insulin deficient) and mice with Type 2 diabetes (insulin resistant).
Researchers found that diabetic animals in both models exhibited learning and memory deficits when cortisol levels were elevated due to impaired plasticity and declines in new cell growth. Returning the levels to normal, however, reversed the negative impact on the hippocampus and restored learning and memory.
“This advance in our understanding of the physiological changes caused by excessive production of cortisol may eventually play a role in preventing and treating cognitive decline in diabetes,” said Mattson, who heads the NIA’s Laboratory of Neurosciences. He and Stranahan explained these findings may also help explain the connection between stress-related mood disorders and diabetes found in human population studies.
糖尿病能否损害人类认知健康是未知的。但现在科学家们鉴定了一种可能影响学习和记忆功能减退的机制。一项新的国家卫生研究所（NIH）对啮齿类动物糖尿病的研究发现肾上腺产生的应激激素水平的升高能扰乱海马的健康功能。海马是脑负责学习和短期记忆的部位。而且当肾上腺糖皮质激素皮质脂酮水平（在人体为氢化考的松）恢复到正常时，海马产生新细胞的能力得以恢复。同时需要补偿损伤、疾病和调节改变的“可塑性”得到恢复。
这项研究在2008年2月17日的《自然神经科学》杂志发表。该杂志是NIH的一部分，由国家老年研究所（NIA）主管。NIA的心理学博士Mark Mattson和同仁们在其研究所的内部研究规划完成了这项研究。研究人员还有Alexis M. Stranahan，是新泽西州普林斯顿大学的毕业生。
“有趣的是这项动物模型研究有可能为阻止和治疗认知损伤提出新的方法。即通过维持正常水平的糖皮质激素来完成，” NIA主任Richard J. Hodes医学博士说，“更进一步的研究将对神经系统、激素和认知健康之间复杂的相互作用提供较好的理解。”
下丘脑-垂体轴（HPA）控制氢化考的松的合成。HPA一个激素产生系统，包括下丘脑和腺垂体及肾脏旁边的肾上腺。血糖控制不好的糖尿病患者通常有一个过度活跃的HPA，肾上腺产生过多氢化考的松。为了研究兴奋性应激激素和海马功能之间的相互作用，研究人员检测认知能力并检验动物模型的脑组织。动物模型用1型糖尿病（胰岛素缺乏）大鼠和2型糖尿病（胰岛素抵抗）小鼠。
研究人员发现，当激素水平升高时，由于可逆性损伤和和新生细胞生长的衰退，两组糖尿病动物模型均显示出学习和记忆缺陷。
“这是我们了解由产生过多氢化考的松引起生理变化的进步，这项进展最终会在阻止和治疗糖尿病患者认知功能减退方面起作用，” 领导NIA神经科学实验室的Mattson说。他和Stranahan解释那些发现也可以说明压力相关的情绪紊乱和基于人类种群的糖尿病之间的关系。
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