Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain.
J Pineal Res. 2010 Mar;48(2):170-7. doi: 10.1111/j.1600-079X.2009.00741.x. Epub 2010 Jan 17.
Melatonin has an important role in the aging process as a potential drug to relieve oxidative damage, a likely cause of age-associated brain dysfunction. As age advances, the nocturnal production of melatonin decreases potentially causing physiological alterations. The present experiments were performed to study in vivo the effects of exogenously administered melatonin chronically on monoaminergic central neurotransmitters serotonin (5-HT), dopamine (DA) and norepinephrine (NE) and behavioral tests in old rats. The accumulation of 5-hydroxy-tryptophan (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 rat brain. Also neurotransmitters 5-HT, DA and NE and some metabolites were quantified by HPLC. In control rats, an age-related decline was observed in neurochemical parameters. However, chronic administration of melatonin (1 mg/kg/day, diluted in drinking water, 4 wk) significantly reversed the age-induced deficits in all the monoaminergic neurotransmitters studied. Also, neurochemical parameters were analyzed after administration of melatonin biosynthesis precursor L-tryptophan (240 mg/kg/day, i.p., at night for 4 wk) revealing similar improvement effects to those induced by melatonin. Behavioral data corresponded well with the neurochemical findings since spatial memory test in radial-maze and motor coordination in rota-rod were significantly improved after chronic melatonin treatment. In conclusion, these in vivo findings suggest that melatonin and L-tryptophan treatments exert a long-term effect on the 5-HT, DA and NE neurotransmission by enhancing monoamine synthesis in aged rats, which might improve the age-dependent deficits in cognition and motor coordination.
褪黑素在衰老过程中作为一种缓解氧化损伤的潜在药物发挥着重要作用，氧化损伤可能是与年龄相关的大脑功能障碍的原因。随着年龄的增长，褪黑素的夜间分泌量减少，可能导致生理变化。本实验旨在研究外源性褪黑素慢性给药对老年大鼠中枢单胺能神经递质 5-羟色胺（5-HT）、多巴胺（DA）和去甲肾上腺素（NE）的体内影响以及行为测试。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大鼠脑中天冬氨酸和酪氨酸羟化率的衡量标准。此外，通过 HPLC 定量测定神经递质 5-HT、DA 和 NE 及一些代谢物。在对照组大鼠中，观察到与年龄相关的神经化学参数下降。然而，褪黑素（1mg/kg/天，溶于饮用水中，连续 4 周）的慢性给药显著逆转了所有研究的单胺能神经递质的年龄诱导缺陷。此外，在给予褪黑素生物合成前体 L-色氨酸（240mg/kg/天，夜间腹腔注射，连续 4 周）后分析神经化学参数，显示出与褪黑素诱导的相似的改善效果。行为数据与神经化学发现非常吻合，因为在放射迷宫中的空间记忆测试和在转棒中的运动协调能力在慢性褪黑素治疗后均得到显著改善。总之，这些体内发现表明，褪黑素和 L-色氨酸治疗通过增强老年大鼠中单胺的合成对 5-HT、DA 和 NE 神经传递发挥长期作用，这可能改善与年龄相关的认知和运动协调缺陷。
