Michałek H, Fortuna S, Volpe M T, Pintor A
Laboratory of Pharmacology, Istituto Superiore di Sanità, Roma, Italy.
Acta Neurobiol Exp (Wars). 1990;50(4-5):237-49.
The recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor sites (MAChRs) following a reduction due to a repeated treatment (2 weeks) with the antiChE agent, isofluorophate (diisopropyl fluorophosphate, DFP) was studied in young (3 months) and aged (24 months) male Sprague-Dawley rats. At the end of DFP treatment the inhibition of ChE in the cerebral cortex, hippocampus and striatum did not differ between young and aged rats (about 70%); the down-regulation of MAChRs (without changes in affinity) varied from 20 to 40% for various areas of brains of rats belonging to the two age-groups, and was the most pronounced in the cerebral cortex of aged rats. As assessed by factorial analysis of variance (2 ages x 2 recoveries ANOVA) there were age-related differences in the recovery rate of both ChE and MAChRs during 5 weeks from the end of DFP treatment. The impairment of recovery observed in aged rats was present in three brain areas and was the most pronounced in the cerebral cortex. Choline acetyltransferase (ChAT) was not influenced by the age and/or treatment in the cerebral cortex and hippocampus while in the striatum an age-related decline was observed. The overall data appear of interest in relation to the recent use of antiChE organophosphorus compounds in the therapy of age-related memory disorders.
在年轻（3个月）和老年（24个月）雄性Sprague-Dawley大鼠中，研究了抗胆碱酯酶药物异氟磷（二异丙基氟磷酸酯，DFP）重复治疗（2周）导致脑胆碱酯酶活性（ChE）和毒蕈碱型乙酰胆碱受体位点（MAChRs）降低后的恢复率。在DFP治疗结束时，年轻和老年大鼠大脑皮质、海马体和纹状体中ChE的抑制率无差异（约70%）；两个年龄组大鼠不同脑区MAChRs的下调（亲和力无变化）在20%至40%之间，且在老年大鼠的大脑皮质中最为明显。通过方差分析（2个年龄×2种恢复情况的方差分析）评估，从DFP治疗结束起的5周内，ChE和MAChRs的恢复率均存在与年龄相关的差异。老年大鼠中观察到的恢复受损存在于三个脑区，且在大脑皮质中最为明显。胆碱乙酰转移酶（ChAT）在大脑皮质和海马体中不受年龄和/或治疗的影响，而在纹状体中观察到与年龄相关的下降。这些总体数据对于近期抗胆碱酯酶有机磷化合物在治疗与年龄相关的记忆障碍中的应用而言似乎很有意义。
