Pazo David, Cardinali Daniel P, Cano Pilar, Reyes Toso Carlos A, Esquifino Ana I
Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurosignals. 2002 Mar-Apr;11(2):81-7. doi: 10.1159/000058544.
The 24-hour rhythms of pineal norepinephrine (NE) content and serotonin (5-HT) turnover [estimated from the ratio of 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT] were studied in young (2 months) and aged (18-20 months) Wistar rats killed at 6 different time points throughout a 24-hour cycle. In the first study, significant changes dependent on the time of day were identified, with acrophases in the first half of the activity span for both parameters. Old rats showed significantly smaller mesor and amplitude of the 24-hour rhythm of pineal NE content. They also showed decreased amplitude of the pineal 5-HT turnover rhythm, in the absence of changes in mesor. In old rats, pineal 5-HT and 5-HIAA concentrations were 41-47% of those found in young rats. In a second study, young and old rats received daily intraperitoneal injections of melatonin (30 microg) or vehicle for 11 days at 19.00 h (i.e. 11 h after light on). Analyzed as a main factor in a factorial analysis of variance, both pineal NE content and 5-HT turnover decreased in old rats while pineal 5-HT turnover increased after melatonin treatment. Melatonin treatment augmented the amplitude of the 24-hour rhythm of pineal NE content by 120 and 52% in young and old rats, respectively. The amplitude of the 24-hour rhythm of pineal 5-HT turnover almost doubled after melatonin treatment in young rats and did not change in old rats. Melatonin injection did not modify the rhythm's acrophase. The results indicate that old rats had lower amplitude and lower mesor values of 24-hour variations in pineal NE content and 5-HT turnover. Melatonin treatment only partly restored pineal NE content and was devoid of activity on pineal 5-HT turnover and 5-HT and 5-HIAA concentration in old rats. Impairment of pineal melatonin synthesizing capacity and intrapineal responses to melatonin may underlie pineal aging in rats.
在整个24小时周期的6个不同时间点处死年轻（2个月）和老年（18 - 20个月）的Wistar大鼠，研究松果体去甲肾上腺素（NE）含量和5-羟色胺（5-HT）周转率[根据5-羟吲哚乙酸（5-HIAA）与5-HT的比率估算]的24小时节律。在第一项研究中，发现了依赖于一天中时间的显著变化，两个参数的活动高峰均出现在活动期的前半段。老年大鼠松果体NE含量的24小时节律的中值和振幅显著较小。它们还表现出松果体5-HT周转率节律的振幅降低，而中值没有变化。老年大鼠松果体5-HT和5-HIAA浓度是年轻大鼠的41 - 47%。在第二项研究中，年轻和老年大鼠于19:00（即光照后11小时）每天腹腔注射褪黑素（30微克）或溶剂，持续11天。在方差分析的析因分析中作为主要因素分析，老年大鼠的松果体NE含量和5-HT周转率均降低，而褪黑素治疗后松果体5-HT周转率增加。褪黑素治疗分别使年轻和老年大鼠松果体NE含量的24小时节律振幅增加了120%和52%。年轻大鼠褪黑素治疗后松果体5-HT周转率的24小时节律振幅几乎翻倍，老年大鼠则没有变化。褪黑素注射未改变节律的高峰相位。结果表明，老年大鼠松果体NE含量和5-HT周转率的24小时变化的振幅和中值较低。褪黑素治疗仅部分恢复了老年大鼠的松果体NE含量，对其松果体5-HT周转率以及5-HT和5-HIAA浓度没有作用。松果体褪黑素合成能力的损害以及松果体内对褪黑素的反应可能是大鼠松果体衰老的基础。
