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急性、不可控应激的神经化学和行为后果:膳食酪氨酸的影响。

Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine.

作者信息

Lehnert H, Reinstein D K, Strowbridge B W, Wurtman R J

出版信息

Brain Res. 1984 Jun 15;303(2):215-23. doi: 10.1016/0006-8993(84)91207-1.

Abstract

Acute, uncontrollable stress increases norepinephrine (NE) turnover in the rat's brain (thereby depleting NE) and diminishes the animal's subsequent tendency to explore a novel environment. We determined whether supplemental dietary tyrosine could prevent some of these changes. Rats given a control diet or diets enriched with tyrosine or tyrosine plus valine were exposed to tail-shock stress or to no stress over a 60-min period. Exposure to the stress caused an increase in NE turnover, decreasing NE and increasing 3-methoxy-4-hydroxy-phenylethylene glycol sulfate (MHPG-SO4) concentrations within the locus coeruleus, hypothalamus and hippocampus. No changes were detected in serotonin (5-HT) levels or turnover. Behavioral deficits following the stress were observed using measures of locomotion and of exploration in a novel open-field environment: stressed animals displayed much less spontaneous motor activity, hole-poking or frequency of standing on their hind legs than control animals. Animals receiving the tyrosine-enriched diet displayed neither the stress-induced depletion of NE nor the behavioral depression. These preventive effects of tyrosine were abolished by co-administration of valine, a large neutral amino acid that competes with tyrosine for transport across the blood-brain barrier. Since tyrosine alone, in animals not subjected to stress, did not change NE turnover nor the behaviors studied, our observations affirm that catecholaminergic neurons respond to the precursor amino acid only when they are physiologically active. Supplementary tyrosine may be useful therapeutically in people exposed chronically to stress.

摘要

急性、无法控制的应激会增加大鼠大脑中去甲肾上腺素(NE)的周转率(从而消耗NE),并降低动物随后探索新环境的倾向。我们确定了补充膳食酪氨酸是否可以预防其中一些变化。给大鼠喂食对照饮食或富含酪氨酸或酪氨酸加缬氨酸的饮食,在60分钟内使其受到尾部电击应激或无应激。暴露于应激会导致NE周转率增加,蓝斑、下丘脑和海马体内的NE减少,3-甲氧基-4-羟基苯乙二醇硫酸盐(MHPG-SO4)浓度增加。血清素(5-HT)水平或周转率未检测到变化。使用新的旷场环境中的运动和探索测量方法观察应激后的行为缺陷:应激动物的自发运动活动、戳洞或后腿站立频率比对照动物少得多。接受富含酪氨酸饮食的动物既没有出现应激诱导的NE消耗,也没有出现行为抑郁。酪氨酸的这些预防作用被缬氨酸共同给药所消除,缬氨酸是一种大中性氨基酸,与酪氨酸竞争穿过血脑屏障的转运。由于单独的酪氨酸在未受应激的动物中不会改变NE周转率或所研究的行为,我们的观察结果证实,儿茶酚胺能神经元仅在其生理活跃时才对前体氨基酸作出反应。补充酪氨酸在长期暴露于应激的人群中可能具有治疗作用。

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