Bahi Amine, Dreyer Jean-Luc
Department of Anatomy, Tawam Medical Campus, United Arab Emirates University, Al Ain, UAE.
Division of Biochemistry, Department of Medicine, University of Fribourg, 1700, Fribourg, Switzerland.
Psychopharmacology (Berl). 2017 Jun;234(12):1829-1840. doi: 10.1007/s00213-017-4588-7. Epub 2017 Mar 16.
Myelin Transcription Factor 1 (MyT1), a member of the Zinc Finger gene family, plays a fundamental role in the nervous system. Recent research has suggested that this transcription factor is associated with the pathophysiology of psychiatric disorders including addiction, schizophrenia, and depression. However, the role of MyT1 in anxiety- and ethanol-related behaviors is still unknown.
We evaluated the effects of lentiviral-mediated overexpression of MyT1 in the dentate gyrus (DG) on anxiety- and ethanol-related behaviors in rats.
We used the elevated plus maze (EPM) and the open field (OF) tests to assess anxiety-like behavior and a two-bottle choice procedure to measure the effects of MyT1 on ethanol intake and preference.
MyT1 overexpression produced anxiolytic-like effects in the EPM test and decreased the number of fecal boli in the OF test, without affecting locomotor activity in both behavioral tests. Next, we demonstrated that ethanol intake and preference were decreased in the MyT1-overexpressing rats with no effect on saccharin and quinine, used to assess taste discrimination, and no effect on ethanol clearance suggesting specific alterations in the rewarding effects of ethanol. Most importantly, ectopic MyT1 overexpression increased both MyT1 and BDNF mRNA levels in the DG. Using Pearson's correlation, results showed a strong negative relationship between MyT1 mRNA and anxiety parameters and ethanol consumption and a positive correlation between MyT1 and BDNF mRNAs.
Taken together, MyT1 along with being a key component in anxiety may be a suitable candidate in the search of the molecular underpinnings of alcoholism.
髓磷脂转录因子1（MyT1）是锌指基因家族的成员，在神经系统中发挥着重要作用。最近的研究表明，这种转录因子与包括成瘾、精神分裂症和抑郁症在内的精神疾病的病理生理学有关。然而，MyT1在焦虑和乙醇相关行为中的作用仍然未知。
我们评估了慢病毒介导的齿状回（DG）中MyT1过表达对大鼠焦虑和乙醇相关行为的影响。
我们使用高架十字迷宫（EPM）和旷场试验（OF）来评估焦虑样行为，并使用双瓶选择程序来测量MyT1对乙醇摄入和偏好的影响。
MyT1过表达在EPM试验中产生抗焦虑样作用，并减少了OF试验中的粪便颗粒数量，而在这两种行为试验中均不影响运动活动。接下来，我们证明，MyT1过表达的大鼠乙醇摄入量和偏好降低，对用于评估味觉辨别力的糖精和奎宁没有影响，对乙醇清除率也没有影响，这表明乙醇的奖赏效应发生了特定改变。最重要的是，异位MyT1过表达增加了DG中MyT1和脑源性神经营养因子（BDNF）的mRNA水平。使用Pearson相关性分析，结果显示MyT1 mRNA与焦虑参数和乙醇消耗之间存在强烈的负相关，而MyT1与BDNF mRNA之间存在正相关。
综上所述，MyT1可能不仅是焦虑的关键组成部分，而且可能是寻找酒精中毒分子基础的合适候选者。
