Undie A S, Friedman E
Department of Psychiatry, Medical College of Pennsylvania.
J Gerontol. 1993 Mar;48(2):B62-7. doi: 10.1093/geronj/48.2.b62.
Receptor-activated hydrolysis of [3H]inositol-labeled phosphoinositides was evaluated in brain slices of 6-month-old (6M) and 24-month-old (24M) F344 rats that had been fed ad libitum (AL) or restricted (60% of normal) diet (RD). The muscarinic cholinergic agonist, carbachol, and the dopamine receptor agonist, SKF3893, stimulated significantly lower accumulation of [3H]inositol phosphates in striatal and cortical slices of the 24M AL rats compared to the 6M AL group. This observation suggests a decreased capacity of the aged brain to respond to receptor-activated phosphoinositide hydrolysis. Furthermore, the 24M RD tissues gave significantly higher responses to carbachol (p < .01) or SKF38393 (p < .01) compared to the 24M AL group. The 24M RD responses were not significantly different from corresponding responses in the 6M AL rats, implying complete prevention of the aging effect in the diet-restricted animals up to at least 24 months of age. Concomitant observations of decreased phosphoinositide labeling in the 24M AL tissues and prevention of this decrease in diet restriction may contribute to the observed effects of aging on inositol phosphate formation.
在随意进食(AL)或限制饮食(正常量的60%,即RD)的6月龄(6M)和24月龄(24M)F344大鼠的脑片中,评估了受体激活的[3H]肌醇标记的磷酸肌醇的水解情况。与6M AL组相比,毒蕈碱胆碱能激动剂卡巴胆碱和多巴胺受体激动剂SKF3893刺激24M AL大鼠纹状体和皮质切片中[3H]肌醇磷酸的积累显著降低。这一观察结果表明,衰老大脑对受体激活的磷酸肌醇水解反应的能力下降。此外,与24M AL组相比,24M RD组织对卡巴胆碱(p <.01)或SKF38393(p <.01)的反应显著更高。24M RD组的反应与6M AL大鼠的相应反应无显著差异,这意味着在至少24月龄的饮食限制动物中,衰老效应得到了完全预防。同时观察到24M AL组织中磷酸肌醇标记减少,而饮食限制可防止这种减少,这可能有助于解释衰老对肌醇磷酸形成的影响。