Gozlan H, Daval G, Verge D, Spampinato U, Fattaccini C M, Gallissot M C, el Mestikawy S, Hamon M
INSERM U288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médicine Pitié-Salpêtrière, Paris, France.
Neurobiol Aging. 1990 Jul-Aug;11(4):437-49. doi: 10.1016/0197-4580(90)90011-n.
Measurements of endogenous levels of serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC), and biochemical and autoradiographic investigations on 5-HT and DA receptors were made in various brain regions in male rats at three different ages: 3 months, 10 months and 22 months. Age-dependent decreases in 5-HT levels associated with parallel increases in 5-HIAA/5-HT ratio were observed in the hypothalamus, striatum, hippocampus and cerebral cortex, suggesting an accelerated 5-HT turnover in aged rats. Similarly, DA levels were lower, and DOPAC/DA ratio was higher in the striatum of 22-month-old compared to 3-month-old or 10-month-old rats. Of the three different classes of 5-HT receptors which were examined, 5-HT1B sites exhibited the largest age-dependent decrease in density, followed by 5-HT2 sites, while 5-HT1A sites remained practically unchanged during aging. By comparison, the loss of striatal D2 receptors in 22-month-old rats compared to young adults was much greater than that of any 5-HT receptor subtype. Such differential age-dependent alterations of the various classes of 5-HT receptors and of dopaminergic versus serotoninergic synaptic markers might be responsible for at least some of the functional deficits in aged animals.
对3个月、10个月和22个月大的雄性大鼠不同脑区的血清素(5-羟色胺,5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)和二羟基苯乙酸(DOPAC)的内源性水平进行了测量,并对5-HT和DA受体进行了生化和放射自显影研究。在下丘脑、纹状体、海马体和大脑皮层中观察到5-HT水平随年龄增长而下降,同时5-HIAA/5-HT比值相应升高,这表明老年大鼠的5-HT周转率加快。同样,与3个月或10个月大的大鼠相比,22个月大的大鼠纹状体中的DA水平较低,而DOPAC/DA比值较高。在所检测的三种不同类型的5-HT受体中,5-HT1B位点的密度随年龄增长下降幅度最大,其次是5-HT2位点,而5-HT1A位点在衰老过程中基本保持不变。相比之下,与年轻成年大鼠相比,22个月大的大鼠纹状体中D2受体的损失比任何5-HT受体亚型都要大得多。各类5-HT受体以及多巴胺能与血清素能突触标记物的这种不同的年龄依赖性变化可能至少是老年动物某些功能缺陷的原因。