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长期生长激素治疗对老年大鼠单胺能神经递质传递及相关行为测试的改善作用。

Improving effects of long-term growth hormone treatment on monoaminergic neurotransmission and related behavioral tests in aged rats.

机构信息

Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain.

出版信息

Rejuvenation Res. 2010 Dec;13(6):707-16. doi: 10.1089/rej.2010.1053. Epub 2011 Jan 5.

DOI:10.1089/rej.2010.1053
PMID:21208059
Abstract

An age-related decline in cognitive functions and physical performance has been associated with reductions in growth hormone (GH) secretion and brain neurotransmitter function. In vivo experiments were performed to study the long-term effects of exogenously administered GH on the central monoaminergic neurotransmitters serotonin, dopamine, and noradrenaline and behavioral tests in old Wistar rats. The accumulation of 5-hydroxytryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of the rate of tryptophan and tyrosine hydroxylation in vivo. Also, the content of the neurotransmitters serotonin, dopamine, and noradrenaline and some metabolites was measured by high-pressure liquid chromatography (HPLC) in the hippocampus and striatum, brain regions involved in adult memory processing and motor coordination. The age-related decline observed in all the neurochemical parameters in control rats was significantly reversed after repeated subcutaneous administration of GH (2 mg/kg per day, 4 weeks). Thus, GH treatment exerted a long-term effect on serotonin, dopamine, and noradrenaline neurotransmission by enhancing neurotransmitter synthesis and metabolism in aged rats. The results obtained after examining working memory tasks in the eight-radial maze and motor ability in the Rotarod treadmill in aged rats were consistent with these neurochemical data; both tests were significantly improved after chronic GH treatment. Overall, these in vivo findings suggest that the positive effects induced by GH on serotonin, dopamine, and noradrenaline neurotransmitters might explain, at least in part, the effects of chronic GH treatment in improving cognitive and motor ability in aged rats, and could aid in preventing or delaying deficits in monoamines associated with learning or motor disabilities.

摘要

随着生长激素(GH)分泌和脑神经递质功能的降低,认知功能和身体机能与年龄相关的衰退已经与之相关。进行了体内实验,以研究外源性给予 GH 对中枢单胺能神经递质血清素、多巴胺和去甲肾上腺素的长期影响以及老年 Wistar 大鼠的行为测试。5-羟色氨酸(5-HTP)和 L-3,4-二羟苯丙氨酸(DOPA)在脱羧酶抑制后的积累被用作体内色氨酸和酪氨酸羟化率的测量。此外,通过高效液相色谱法(HPLC)测量神经递质血清素、多巴胺和去甲肾上腺素以及一些代谢物的含量,在海马体和纹状体中,这些脑区参与成年记忆处理和运动协调。在对照大鼠中观察到的与年龄相关的所有神经化学参数的下降在重复皮下给予 GH(每天 2 毫克/公斤,4 周)后显著逆转。因此,GH 治疗通过增强老年大鼠神经递质的合成和代谢对血清素、多巴胺和去甲肾上腺素的神经传递产生长期影响。在老年大鼠的八臂迷宫中检查工作记忆任务和在旋转棒跑步机中检查运动能力后获得的结果与这些神经化学数据一致;慢性 GH 治疗后这两项测试均显著改善。总体而言,这些体内发现表明,GH 对血清素、多巴胺和去甲肾上腺素神经递质的积极影响至少部分解释了慢性 GH 治疗改善老年大鼠认知和运动能力的作用,并有助于预防或延迟与学习或运动障碍相关的单胺类物质的缺陷。

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