Undie A S, Friedman E
Department of Psychiatry, Medical College of Pennsylvania, Philadelphia 19129.
Neurobiol Aging. 1992 Jul-Aug;13(4):505-11. doi: 10.1016/0197-4580(92)90079-d.
Accumulation of [3H]inositol phosphate and [3H]inositol labeling of phosphoinositides were evaluated in brain slices of 3-, 6-, 12-, and 24-month-old Fischer-344 rats. The dopamine agonist, SKF38393, stimulated significantly lower accumulations of inositol trisphosphate, inositol bisphosphate, and inositol monophosphate in the striatum, hippocampus, and frontal cortex of 24-month-old rats compared with the 6-month-old animals. No differences, however, were observed between the 3, 6, and 12-month-old groups. Furthermore there were marked decrements of 41% to 58% in the labeling of phosphoinositides in the different brain regions of the aged animals. Dose-response studies in forebrain slices of the 6-month-old and 24-month-old animals showed aging-related decrements of 53% (p less than 0.001) and 48% (p less than 0.001) in the maximal SKF38393-stimulated labeling of phosphoinositides and accumulation of inositol phosphates, respectively. These data suggest that aging of the rat brain is associated with alterations in the basal turnover of the inositol cycle and in the sensitivity of the transduction pathway to dopamine receptor stimulation.
在3个月、6个月、12个月和24个月大的Fischer-344大鼠的脑片中评估了[3H]肌醇磷酸的积累和磷酸肌醇的[3H]肌醇标记。与6个月大的动物相比，多巴胺激动剂SKF38393在24个月大的大鼠纹状体、海马体和额叶皮质中显著降低了肌醇三磷酸、肌醇二磷酸和肌醇单磷酸的积累。然而，在3个月、6个月和12个月大的组之间未观察到差异。此外，老年动物不同脑区的磷酸肌醇标记有41%至58%的显著下降。对6个月大与24个月大动物的前脑片进行的剂量反应研究表明，在SKF38393刺激下，磷酸肌醇的最大标记和肌醇磷酸的积累分别出现与衰老相关的53%（p小于0.001）和48%（p小于0.001）的下降。这些数据表明，大鼠大脑衰老与肌醇循环的基础周转率变化以及转导途径对多巴胺受体刺激的敏感性变化有关。
