PDF(Pubmed)
Abstract：
Most HIV-antiretroviral drugs have adverse effects. Efavirenz (EFV) is an example of a drug with neuropsychiatric effects, such as anxiety, depression, and suicidal thoughts, in people living with HIV (PLWH). The mechanisms by which EFV causes neuropsychiatric alterations in PLWH are complex, multifactorial, and not fully understood, although several studies in animals have reported changes in brain energy metabolism, alterations in monoamine turnover, GABA, and glutamate levels, and changes in 5-HT receptors. In this report, we studied the effects of EFV on the serotonergic system in healthy mice, specifically, whether EFV results in alterations in the levels of the tryptophan hydroxylase 2 (Tph2) gene in the brain. EFV (10 mg/kg) and distilled water (1.5 µL/kg) (control group) were orally administered to the mice for 36 days. At the end of the treatment, Tph2 expression levels in mouse brains were measured, and mood was evaluated by three trials: the forced swim test, elevated plus maze, and open field test. Our results revealed dysregulation of Tph2 expression in the brainstem, amygdala, and hypothalamus in the EFV group, and 5-HT levels increased in the amygdala in the EFV group. In the behavioral tests, mice given EFV exhibited a passive avoidance response in the forced swim test and anxiety-like behavior in the elevated plus maze, and they lost weight. Herein, for the first time, we showed that EFV triggered dysregulation of the Tph2 gene in the three serotonergic areas studied; and 5-HT levels increased in the amygdala using the ELISA method. However, further studies will be necessary to clarify the increase of 5-HT in the amygdala as well as understand the paradoxical decrease in body weight with the simultaneous increase in food consumption. It will also be necessary to measure 5-HT by other techniques different from ELISA, such as HPLC.
摘要：
大多数HIV抗逆转录病毒药物都有副作用。Efavirenz（EFV）是具有神经精神作用的药物的一个例子，比如焦虑，抑郁症,和自杀的想法，艾滋病毒感染者（PLWH）。EFV引起PLWH神经精神改变的机制是复杂的，多因素，并没有完全理解，尽管一些动物研究报告了大脑能量代谢的变化，单胺周转的改变，GABA,和谷氨酸水平，和5-HT受体的变化。在这份报告中,我们研究了EFV对健康小鼠血清素能系统的影响，具体来说,EFV是否导致大脑中色氨酸羟化酶2（Tph2）基因水平的改变。将EFV(10mg/kg)和蒸馏水(1.5μL/kg)(对照组)口服给予小鼠36天。在治疗结束时,测量小鼠大脑中Tph2的表达水平，通过三个试验来评估情绪：强迫游泳测试，高架加上迷宫，和开放现场测试。我们的结果揭示了脑干中Tph2表达的失调，杏仁核,EFV组的下丘脑，EFV组杏仁核中5-HT水平升高。在行为测试中，给予EFV的小鼠在强迫游泳测试中表现出被动回避反应，在高架迷宫中表现出焦虑样行为，他们减肥了.在这里，第一次,我们发现EFV在所研究的三个5-羟色胺能区域中触发了Tph2基因的失调；使用ELISA方法，杏仁核中的5-HT水平升高。然而,需要进一步的研究来阐明杏仁核中5-HT的增加，并了解体重的矛盾下降与食物消耗的同时增加。还需要通过不同于ELISA的其他技术来测量5-HT。如HPLC。
