Gibson G E, Peterson C
J Neurochem. 1981 Oct;37(4):978-84. doi: 10.1111/j.1471-4159.1981.tb04484.x.
Acetylcholine (ACh) synthesis in vivo is known to decrease during the aging process (senescence). To elucidate the molecular mechanism(s) of this age-related decline, we studied brain slices from 3-, 10-, and 30-month-old mice of two strains (C57B1 and Balb/c). In low K+ media, oxidative metabolism as measured by 14CO2 production decreased with aging from 100% (3 months) to 85% (10 months) or 71% (30 months) whether [U-14C]glucose, [3,4-14C]glucose, or [1-14C]pyruvate was the substrate. In the aged brain (30 months) the increase in 14CO2 production with K+ stimulation was about twofold higher than in the young brain (3 months). Thus, in high K+ media, only slight decreases (less than 10%) in oxidative metabolism occurred with aging. Changes in ACh synthesis paralleled the decreases in 14CO2 production. Synthesis of [14C]ACh from [U-14C]glucose in low K+ media declined from 100% (3 months) to 85% (10 months) or 66% (30 months), while in high K+ media only slight decreases (less than 10.5%) occurred with aging. The Ca2+-dependent, K+-stimulated release of [14C]ACh declined from 100% (3 months) to 58% (10 months) or 25% (30 months). Only the decrease in he release of ACh declined to the same extent as the reduced in vivo synthesis of ACh with aging. The results suggest that decreases in oxidative metabolism, ACh synthesis, and in the release of ACh contribute to a reduction in cholinergic function in senescent brain.
已知体内乙酰胆碱（ACh）的合成在衰老过程中会减少。为了阐明这种与年龄相关的下降的分子机制，我们研究了两种品系（C57B1和Balb/c）3个月、10个月和30个月大的小鼠的脑片。在低钾培养基中，无论底物是[U-14C]葡萄糖、[3,4-14C]葡萄糖还是[1-14C]丙酮酸，通过14CO2产生所测量的氧化代谢随着衰老从100%（3个月）降至85%（10个月）或71%（30个月）。在老年脑（30个月）中，钾离子刺激引起的14CO2产生的增加比年轻脑（3个月）高约两倍。因此，在高钾培养基中，随着衰老氧化代谢仅略有下降（小于10%）。乙酰胆碱合成的变化与14CO2产生的减少平行。在低钾培养基中，由[U-14C]葡萄糖合成[14C]乙酰胆碱从100%（3个月）降至85%（10个月）或66%（30个月），而在高钾培养基中随着衰老仅略有下降（小于10.5%）。钙离子依赖性、钾离子刺激的[14C]乙酰胆碱释放从100%（3个月）降至58%（10个月）或25%（30个月）。只有乙酰胆碱释放的减少程度与衰老过程中体内乙酰胆碱合成减少的程度相同。结果表明，氧化代谢、乙酰胆碱合成以及乙酰胆碱释放的减少导致衰老脑胆碱能功能降低。
