EFFECT OF NEONATAL HANDLING ON AGE-RELATED IMPAIRMENTS ASSOCIATED WITH THE HIPPOCAMPUS
EFFECT OF NEONATAL HANDLING ON AGE-RELATED IMPAIRMENTS ASSOCIATED WITH THE HIPPOCAMPUS
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DOI：
10.1126/science.3340858
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发表时间：
1988-02-12
期刊：
影响因子：
56.9
通讯作者：
SAPOLSKY, RM
中科院分区：
文献类型：
--
作者：
MEANEY, MJ;AITKEN, DH;SAPOLSKY, RM
在大鼠中，在生命早期发生的环境操纵导致肾上腺皮质轴的变化，这种变化在动物的整个生命过程中持续存在，并减弱了与衰老相关的某些缺陷。在婴儿期处理的大鼠海马中糖皮质激素受体的浓度永久性增加，海马是肾上腺皮质活动负反馈抑制的关键区域。受体浓度的增加导致海马对糖皮质激素的敏感性增加，并增强了处理大鼠的负反馈功效。因此，在所有年龄段的测试中，没有处理的大鼠分泌更多的糖皮质激素来应对压力，而不是处理的大鼠。在以后的年龄，nonhandled大鼠也表现出升高的基础糖皮质激素水平，结果是有一个更大的累积暴露于nonhandled大鼠糖皮质激素。肾上腺糖皮质激素暴露增加可加速海马神经元丢失和衰老中的认知障碍。海马细胞的损失和明显的空间记忆缺陷出现与年龄的nonhandled大鼠，但几乎没有在处理的大鼠。先前的工作表明，糖皮质激素分泌过多，海马神经元死亡和认知障碍形成了一个复杂的退行性级联老化的大鼠。目前的研究表明，在生命早期进行微妙的操纵可以延缓这种级联反应的出现。
In rats, an environmental manipulation occurring early in life resulted in changes in the adrenocortical axis that persisted throughout the entire life of the animals and attenuated certain deficits associated with aging. Rats handled during infancy had a permanent increase in concentrations of receptors for glucocorticoids in the hippocampus, a critical region in the negative-feedback inhibition of adrenocortical activity. Increased receptor concentrations led to greater hippocampal sensitivity to glucocorticoids and enhanced negative-feedback efficacy in the handled rats. Thus, at all ages tested, rats that were not handled secreted more glucocorticoids in response to stress than did handled rats. At later ages, nonhandled rats also showed elevated basal glucocorticoid levels, with the result that there was a greater cumulative exposure to glucocorticoids in nonhandled rats. Increased exposure to adrenal glucocorticoids can accelerate hippocampal neuron loss and cognitive impairments in aging. Hippocampal cell loss and pronounced spatial memory deficits emerged with age in the nonhandled rats, but were almost absent in the handled rats. Previous work showed that glucocorticoid hypersecretion, hippocampal neuron death, and cognitive impairments form a complex degenerative cascade of aging in the rat. The present study shows that a subtle manipulation early in life can retard the emergence of this cascade.