Importance of 11-beta-hydroxysteroid dehydrogenase (HSD-1) in the consequences of chronic alcohol consumption

酒精依赖是一种慢性复发性疾病，据卫生部最近估计，其发病率占成年人口的7%。目前，在设法戒酒的酗酒者中，高达90%的人会在一年内重新酗酒。酒精依赖是一个主要的健康问题，饮酒会导致许多其他的医疗疾病和广泛的社会问题。50%至80%的酗酒者因饮酒而导致记忆问题，许多人还存在其他健康问题，特别是抑郁症。记忆问题不仅对生活质量有严重影响，而且对酗酒者从治疗方案中受益的能力也有严重影响，因为这些方案往往涉及学习新的行为方式。记忆丧失很难治疗，很大程度上是因为导致记忆问题的大脑变化还不清楚。如果了解记忆问题所涉及的机制，这将有助于开发有效的治疗方法，提高酗酒者的生活质量，使他们能够从治疗方案中获得更多好处，并降低医疗成本。最近的实验室和临床研究表明，当一个人停止过度饮酒时，大脑发生的变化在很大程度上导致了记忆缺陷。停止饮酒还会增加大脑中被称为糖皮质激素的应激激素的浓度。众所周知，高浓度的这些激素会对大脑中的神经造成损害，并导致记忆问题。实验室研究表明，阻止糖皮质激素的增加，或阻止这些激素的作用，可以减少因长期饮酒而造成的神经损害。有这种效果的治疗也可以防止戒掉长期饮酒后的记忆力丧失。目前项目的目的是研究大脑糖皮质激素浓度增加的机制，特别是一种名为HSD-1的酶的作用。两种预防HSD-1影响的药物的效果也将被研究，以确定它们是否可以防止长期饮酒和戒酒造成的记忆丧失。这些知识将有助于开发新的治疗方法，为这些问题提供有效的治疗方法，这些问题是大量酗酒者所遭受的。

Alcohol dependence is a chronic relapsing disease, the incidence of which was recently estimated by the Department of Health to be 7% of the adult population. Currently, up to 90% of alcoholics who manage to stop drinking relapse back to the alcohol within a year. Alcohol dependence is a major health problem, and the alcohol consumption causes many other medical disorders and extensive social problems. Between 50 and 80% of alcoholics suffer from memory problems caused by the alcohol consumption and many also have other medical problems, particularly depression. The memory problems have serious effects not only on the quality of life but on the ability of alcoholics to benefit from treatment programmes, since these frequently involve learning new ways of behaviour. The memory loss is very difficult to treat, largely because the changes in the brain that cause the memory problems are not yet understood. If the mechanisms involved in the memory problems are understood, this will enable effective treatments to be developed that will improve quality of life for alcoholics, enable them to obtain more benefit from treatment programmes and reduce health costs. Recent laboratory and clinical studies have suggested that changes in the brain that take place when someone stops drinking excessively are largely responsible for memory deficits. Stopping alcohol drinking also increase the concentrations in the brain of stress hormones known as glucocorticoids. High concentrations of these are known to cause damage to nerves in the brain, and to result in memory problems.Laboratory studies have shown that prevention of the increases in glucocorticoid hormones, or prevention of the actions of these hormones, decreases the nerve damage caused by cessation of long term alcohol consumption. Treatments which have this effect also prevented the memory loss see after withdrawal from chronic alcohol consumption. The aim of the current project is to investigate the mechanism of the increases in brain glucocorticoid concentrations, in particular the role of an enzyme, called HSD-1. The effects of two drugs that prevent the effects of HSD-1 will also be studied to see if these prevent the memory loss caused by long-term alcohol intake and withdrawal. Such knowledge will aid the development of new treatments that would provide effective therapy for these problems, which are suffered by large numbers of alcoholics.