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Profile of acetylcholinesterase in brain areas of male and female rats of adult and old age.

机译:成年和成年雄性和雌性大鼠脑区域中乙酰胆碱酯酶的概况。

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Inhibition of acetylcholinesterase (AChE)-metabolizing enzyme of acetylcholine, is presently the most important therapeutic target for development of cognitive enhancers. However, AChE activity in brain has not been properly evaluated on the basis of age and sex. In the present study, AChE activity was investigated in different brain areas in male and female Sprague-Dawley rats of adult (3 months) and old (18-22 months) age. AChE was assayed spectrophotometrically by modified Ellman's method. Specific activity (micromoles/min/mg of protein) of AChE was assayed in salt soluble (SS) and detergent soluble (DS) fractions of various brain areas, which consists of predominantly G1 and G4 molecular isoforms of AChE respectively. The old male rats showed a decrease (40-55%) in AChE activity in frontal cortex, striatum, hypothalamus and pons in DS fraction and there was no change in SS fraction in comparison to adult rats. In the old female rats the activity was decreased (25-40%) in frontal cortex, cerebral cortex, striatum, thalamus, cerebellum and medulla in DS fraction whereas in SS fraction the activity was decreased only in hypothalamus as compared to adult. On comparing with old male rats, old female rats showed increase in AChE activity in cerebral cortex, hippocampus and hypothalamus of DS fraction and decrease in hypothalamus of SS fraction. There was a significant increase in AChE activity in DS fraction of cerebral cortex, hippocampus, hypothalamus, thalamus and cerebellum in female as compared to male adult rats. However, no significant change in AChE activity was found in the SS fraction, except hypothalamus between these groups. Thus it appears that age alters AChE activity in different brain regions predominantly in DS fraction (G4 isoform) that may vary in male and female. These observations have significant relevance to age related cognitive deficits and its pharmacotherapy.
机译:抑制乙酰胆碱的乙酰胆碱酯酶(AChE)-代谢酶目前是发展认知增强剂的最重要的治疗靶标。但是,尚未根据年龄和性别正确评估大脑中的AChE活性。在本研究中,对成年(3个月)和大(18-22个月)大的雄性和雌性Sprague-Dawley大鼠的不同大脑区域中的AChE活性进行了研究。 AChE用改良的Ellman方法分光光度法测定。在各个脑区的盐溶性(SS)和去污剂可溶性(DS)馏分中测定AChE的比活度(微摩尔/分钟/毫克蛋白质),该部分分别由AChE的G1和G4分子同工型组成。与成年大鼠相比,成年雄性大鼠的额叶皮层,纹状体,下丘脑和桥脑的AChE活性降低(40-55%),而SS分数没有变化。在成年雌性大鼠中,DS分数中额叶皮质,大脑皮质,纹状体,丘脑,小脑和延髓的活性降低(25-40%),而SS分数中,仅与成人相比,下丘脑的活性降低。与老年雄性大鼠相比,老年雌性大鼠的大脑皮质,海马和下丘脑DS级分的AChE活性增加,而下丘脑SS级分的AChE活性降低。与成年雄性大鼠相比,雌性大鼠大脑皮质,海马,下丘脑,丘脑和小脑的DS分数中的AChE活性显着增加。然而,除这些组之间的下丘脑外,在SS部分中未发现AChE活性的显着变化。因此,年龄似乎改变了不同大脑区域的AChE活性,主要是在DS分数(G4亚型)中,男性和女性可能有所不同。这些观察结果与年龄相关的认知缺陷及其药物治疗具有显着的相关性。

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