Zimatkin S M, Tsydik V F, Lelevich V V
Institute of Biochemistry Academy of Sciences of Belarus, Grodno.
Cas Lek Cesk. 1997 Nov 5;136(21):666-9.
In spite of numerous biochemical studies the role of brain monoamine oxidase (MAO, EC 1.4, 3.4) in the mechanisms of central alcohol action and the pathogenesis of alcoholism remains unclear. The possible reason of that is the highly heterogeneous distribution of the enzyme in a brain and the different direction of alcohol-induced changes of MAO in various morphological structures. Therefore we used the histochemical approach for examination of the effect of chronic alcohol consumption on MAO A and B activities in definite brain structures: various types of aminergic neurons, glial cells and blood capillaries.
For 6 months 180 inbred male rats consumed 15% ethanol as the only source of drinking (mean alcohol consumption was 6 g/kg/day). On the 5-6th months of the experiment animals with maximal (ethanol preferring, EP) or minimal (water preferring, WP) alcohol craving were chosen by testing for free choice between 15% (v/v) ethanol solution and water (3 times, during 2 days, at 2-week intervals). The animals chosen were sacrificed and brain samples were studied by our quantitative histochemical method (23). It was found, that chronic ethanol consumption induced dramatic disturbances in MAO activities in the brain structures strongly depending on the alcohol preference of animals. The total MAO activity in WP rats decreased or remained unchanged, but in EP rats it dramatically increased, especially in neurons of n. raphe pontis and n. raphe dorsalis (1.198 +/- 0.028 and 1.268 +/- 0.018 units as compared to control values 0.594 +/- 0.008 and 0.804 +/- 0.011 units; p < 0.001). MAO A activity in all brain structures containing both forms of the enzyme was increased, especially in EP rats: up to 3 times in neurons of the n. raphe pontis from 0.134 +/- 0.003 units in control to 0.541 +/- 0.013 units; p < 0.001). At the same time in the neurons containing only MAO A activity (n. olivaris superior and n. subcoeruleus) it significantly decreased, especially in WP animals. MAO B activity was reduced in the brain structures of WP rats, but activated or unchanged in EP rats. In all the structures studied the MAO B activity was significantly higher in EP, as compared to WP animals (f.e. in astrocytes: 0.314 +/- 0.012 and 0.200 +/- 0.012 units accordingly, p < 0.001). Despite the significant differences in the degree and direction of the changes in the activity of the MAO forms in rats with different alcohol craving, the calculated share of MAO A in the total MAO activity was regularly increased in all structures studied both in EP and WP animals; the share of MAO B activity accordingly decreased.
Chronic alcohol consumption induces the great disturbances in brain MAO activity and isozyme composition following chronic ethanol consumption, strongly depending of the alcohol craving of the animals. It indicates the involvement of the enzyme in the mechanisms of central alcohol action.
尽管进行了大量的生化研究，但脑单胺氧化酶（MAO，EC 1.4, 3.4）在中枢酒精作用机制和酒精中毒发病机制中的作用仍不清楚。其可能的原因是该酶在脑中分布高度不均一，且在不同形态结构中酒精诱导的MAO变化方向不同。因此，我们采用组织化学方法研究长期饮酒对特定脑结构中MAO A和B活性的影响，这些结构包括各种类型的胺能神经元、胶质细胞和毛细血管。
180只近交系雄性大鼠连续6个月将15%乙醇作为唯一饮水来源（平均酒精摄入量为6 g/kg/天）。在实验的第5 - 6个月，通过在15%（v/v）乙醇溶液和水之间进行自由选择测试（在2天内分3次，间隔2周），挑选出酒精渴望程度最高（乙醇偏好型，EP）或最低（水偏好型，WP）的动物。将挑选出的动物处死后，用我们的定量组织化学方法（23）研究脑样本。结果发现，长期摄入乙醇会导致脑结构中MAO活性出现显著紊乱，这在很大程度上取决于动物的酒精偏好。WP大鼠的总MAO活性降低或保持不变，但EP大鼠的总MAO活性显著增加，尤其是在脑桥中缝核和背侧中缝核的神经元中（分别为1.198±0.028和1.268±0.018单位，而对照值分别为0.594±0.008和0.804±0.011单位；p < 0.001）。在同时含有两种MAO形式的所有脑结构中，MAO A活性均增加，尤其是在EP大鼠中：脑桥中缝核神经元中的MAO A活性从对照的0.134±0.003单位增加至0.541±0.013单位，增加了近3倍；p < 0.001）。同时，在仅含有MAO A活性的神经元（上橄榄核和蓝斑下核）中，MAO A活性显著降低，尤其是在WP动物中。WP大鼠脑结构中的MAO B活性降低，但EP大鼠中的MAO B活性被激活或保持不变。在所有研究的结构中，与WP动物相比，EP动物的MAO B活性显著更高（例如在星形胶质细胞中：分别为0.314±0.012和0.200±0.012单位，p < 0.001）。尽管不同酒精渴望程度的大鼠中MAO形式活性变化的程度和方向存在显著差异，但在EP和WP动物的所有研究结构中，计算得出的MAO A在总MAO活性中的占比均有规律地增加；相应地，MAO B活性的占比降低。
长期饮酒会导致脑MAO活性和同工酶组成出现极大紊乱，这在很大程度上取决于动物的酒精渴望程度。这表明该酶参与了中枢酒精作用机制。
