Michalek H, Pintor A, Fortuna S
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Rome, Italy.
Ann Ist Super Sanita. 1990;26(1):61-8.
In the first part of the investigation the age-related changes in cortical, hippocampal and striatal cholinesterases (ChE), choline acetyltransferase (ChAT) and muscarinic acetylcholine receptors (mAChRs, measured as Bmax of 3H-QNB binding) were compared in male Wistar, Fischer 344 and Sprague-Dawley rats aged 3 and 24 months. Fischer rats exhibited 1.5 fold higher levels of ChAT and mAChRs than Wistar and Sprague-Dawley rats in the areas analyzed. The age-related decline of cortical ChAT and mAChRs was present in Fischer rats but not in those of the other two strains, i.e. was strain-dependent. There were no age-related changes in hippocampal ChAT in any strain. The decline of striatal ChAT, hippocampal and striatal mAChRs and ChE in the three regions analyzed were present in Wistar, Fischer and Sprague-Dawley aged rats. Thus, these deficits (or lack of changes) appeared to be not strain-dependent. The overall data indicate the importance of genotype in the rate of aging, and an accelerated aging for Fischer 344 rats. In the second part of the investigation the responsiveness of cortical mAChRs, ChE and ChAT to a repeated treatment with an indirect cholinergic agonist (an antiChE agent, diisopropyl fluorophosphate-DFP) was studied in two independent experiments on Fischer 344 and Sprague Dawley rats aged 3 and 24 months. The s.c. administration of DFP (first dose 1.6, subsequent six doses of 1.1 mg/kg on alternate days) to senescent Fischer rats caused a considerably more pronounced syndrome of cholinergic stimulation than in young ones, resulting in 60 and 14% mortality, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
在研究的第一部分，比较了3月龄和24月龄雄性Wistar大鼠、Fischer 344大鼠和Sprague-Dawley大鼠皮质、海马和纹状体胆碱酯酶（ChE）、胆碱乙酰转移酶（ChAT）以及毒蕈碱型乙酰胆碱受体（mAChRs，通过³H-QNB结合的Bmax来测定）与年龄相关的变化。在所分析的区域中，Fischer大鼠的ChAT和mAChRs水平比Wistar大鼠和Sprague-Dawley大鼠高1.5倍。Fischer大鼠皮质ChAT和mAChRs随年龄增长而下降，而其他两个品系的大鼠则没有，即这种变化具有品系依赖性。任何品系的海马ChAT均未出现与年龄相关的变化。Wistar大鼠、Fischer大鼠和Sprague-Dawley老年大鼠所分析的三个区域中，纹状体ChAT、海马和纹状体mAChRs以及ChE均出现下降。因此，这些缺陷（或无变化情况）似乎不具有品系依赖性。总体数据表明基因型在衰老速率中的重要性，以及Fischer 344大鼠衰老加速。在研究的第二部分，在两项独立实验中，对3月龄和24月龄的Fischer 344大鼠和Sprague Dawley大鼠，研究了皮质mAChRs、ChE和ChAT对间接胆碱能激动剂（一种抗胆碱酯酶药物，二异丙基氟磷酸酯-DFP）重复治疗的反应性。对衰老的Fischer大鼠皮下注射DFP（首剂1.6 mg/kg，随后六剂每隔日1.1 mg/kg），导致胆碱能刺激综合征比年轻大鼠明显得多，分别导致60%和14%的死亡率。（摘要截短于250词）
