Impairment in Acetylcholinesterase Activity in Different Brain Parts of Female Mice, Mus musculus Following 17 α-Methyltestosterone (Anabolic- Androgenic Steroid)

Sachin Patil, Praveenkumar Kondaguli, L. S. Inamdar
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Abstract

Objective: Anabolic androgenic steroids (AAS) are synthetic derivatives of the male sex hormone testosterone. In the present investigation, we studied the impact of one of the AAS compounds 17\(\alpha\)-methyltestosterone on acethylcholinesterase (AChE) enzyme activity in different parts of mice brain viz. forebrain, hippocampus, midbrain, and hindbrain. Methods: The adult female mice were assigned to four experimental groups to which different doses of 17\(\alpha\)-Methyltestosterone (17\(\alpha\)-MT- 0.5, 5.0 and 7.5 mg/kg bwt, respectively) were administrated s.c. for 30 days. Results: A significant increase in AChE activity in forebrain and midbrain (low and medium dose treatment) suggests a reduction of cholinergic neurotransmission efficiency due to a decrease in acetylcholine levels in the trans-synaptic cleft. Further, a concurrent reduction in AChE activity was observed in the whole brain, hippocampus and hindbrain of 17\(\alpha\)-MT treated mice suggest the impairment in neuronal transmission. Since the regulation of cholinergic system through acetylcholine hydrolysis has been largely attributed to AChE activity, a significant reduction in its activity may lead to stress-related anxiety, memory loss with some cognitive and behavioral aspects in the mice. Conclusion: Based on the observed results we propose that 17\(\alpha\)-MT an alkylated steroid compound has a negative impact on AChE enzyme activity in different parts of mice brain leading to impairment in neuronal transmission.
17 α-甲基睾酮(合成代谢雄激素)对雌性小家鼠不同脑区乙酰胆碱酯酶活性的影响
目的:合成代谢雄激素类固醇(AAS)是雄性激素睾酮的合成衍生物。本实验研究了一种AAS化合物17 \(\alpha\) -甲基睾酮对小鼠前脑、海马、中脑和后脑不同部位乙酰胆碱酯酶(AChE)活性的影响。方法:将成年雌性小鼠分为4个实验组,分别给予不同剂量的17 \(\alpha\) -甲基睾酮(17 \(\alpha\) - mt - 0.5、5.0和7.5 mg/kg bwt),连续30 d。结果:前脑和中脑(低、中剂量治疗)乙酰胆碱酯酶活性显著增加,表明胆碱能神经传递效率降低,这是由于突触间隙中乙酰胆碱水平降低所致。此外,17只\(\alpha\) -MT处理小鼠全脑、海马和后脑同时观察到AChE活性降低,提示神经元传递受损。由于乙酰胆碱水解对胆碱能系统的调节在很大程度上归因于乙酰胆碱酯酶的活性,乙酰胆碱酯酶活性的显著降低可能导致小鼠出现与压力相关的焦虑、认知和行为方面的记忆丧失。结论:基于观察结果,我们提出烷基化类固醇化合物17 \(\alpha\) -MT对小鼠脑不同部位乙酰胆碱酯酶活性有负面影响,导致神经元传递受损。
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