ALCOHOL, BRAIN METABOLISM AND BENZODIAZEPINE RECEPTOR BINDING

死后的神经病理学研究表明， 酒精的摄入减少了上级额叶神经元的数量 大脑皮层的区域。 死后组织的生化研究 长期酒精依赖的受试者表明，GABA- A/苯二氮卓类（BDZ）受体可能在额叶皮层减少 和海马体，但大脑皮层的其他区域没有。 利用 正电子发射断层扫描（PET）与[11 C]氟马西尼，我们建议 确定BDZ受体的密度是否降低， 额叶皮层在生活中的慢性酒精依赖的人， 与一组年龄和性别相似的正常对照组相比， 分布。 使用PET与[18F]氟脱氧葡萄糖在相同的 受试者，我们将检查局部脑葡萄糖代谢率 （LCMRG），并比较BDZ受体结合的分布与 LCMRG模式。 我们预计在慢性酒精依赖者中 患者BDZ受体密度降低， LCMRG在大脑皮层的上级额叶区域。 我们将使用 神经心理学测试不能研究额叶功能， 患者，并预期发现性能降低， 与BDZ受体和LCMRG的减少水平相关， 上级额叶皮层 神经病理学研究还表明，长期摄入过量 乙醇减少了小脑上级蚓部的神经元数量， 小脑，即使对于没有小脑疾病症状的患者也是如此 生活中 慢性肺心病死后组织的生化研究 酒精依赖的受试者表明，BDZ受体结合可能 在小脑中减少。 我们建议使用[11C]氟马西尼， [18 F]氟脱氧葡萄糖与PET检查BDZ受体的密度 和临床症状性LCMRG患者的模式 酒精性小脑变性（ACD），慢性酒精依赖性 无小脑变性证据且正常的患者 年龄和性别分布相似的对照组。 为了检测 任何生物化学变化所造成的解剖连接之间 大脑皮层和小脑，我们也建议研究患者 慢性小脑退化（显性遗传） 橄榄体脑桥小脑萎缩，OPCA）使用相同的PET探头， 确定BDZ结合中的局灶性干扰是否会降低LCMRG 局限于小脑前上级。 我们预计会发现 BDZ结合减少和LCMRG减少仅限于酒精和酒精中， 无ACD的依赖性患者，BDZ结合减少， LCMRG广泛分布于小脑，但不局限于大脑皮质， OPCA患者

Postmortem neuropathological studies indicate that excessive chronic intake of ethanol decreases the number of neurons in the superior frontal region of the cerebral cortex. Biochemical studies on postmortem tissue of chronically alcohol-dependent subjects suggest that GABA- A/benzodiazepine (BDZ) receptors may be decreased in the frontal cortex and hippocampus but not in other areas of the cerebral cortex. Utilizing positrons emission tomography (PET) with [11C]Flumazenil, we propose to determine whether the density of BDZ receptors is reduced within the frontal cortex in living chronically alcohol-dependent persons as compared with a group of normal control subjects with similar age and sex distributions. Using PET with [18F]fluorodeoxyglucose in the same subjects, we will examine the local cerebral metabolic rate for glucose (LCMRG) and compare the distribution of BDZ receptor binding with the pattern of LCMRG. We anticipate finding in chronically alcohol-dependent patients a decrease in the density of BDZ receptors and a decrease in LCMRG in the superior frontal region of the cerebral cortex. We will use neuropsychological tests t study frontal lobe function in the same patients, and anticipate finding that performance is diminished and correlated with the level of reduction of BDZ receptors and of LCMRG in the superior frontal cortex. Neuropathological studies also demonstrate that excessive chronic intake of ethanol decreases the number of neurons in the superior vermis of the cerebellum, even in patients who had no symptoms of cerebellar disorder in life. Biochemical studies on postmortem tissue of chronically alcohol-dependent subjects suggest that BDZ receptor binding may be decreased in the cerebellum. We propose to use [11C]flumazenil and [18F]fluorodeoxyglucose with PET to examine the density of BDZ receptors and the pattern of LCMRG in patients with clinically symptomatic alcoholic cerebellar degeneration (ACD), in chronically alcohol-dependent patients without evidence of cerebellar degeneration and in normal control subjects of similar age and sex distribution. In order to detect any biochemical changes resulting from the anatomical connections between the cerebral cortex and the cerebellum, we also propose to study patients with a chronic cerebellar degeneration (dominantly inherited olivopontocerebellar atrophy, OPCA) using the same PET probes to determine whether focal disturbances in BDZ binding and decrease LCMRG confined to the anterior superior cerebellum. We anticipate finding decreased BDZ binding and decreased LCMRG confined to and in alcohol- dependent patients without ACD, and reduced BDZ binding and decreased LCMRG widely i the cerebellum but not focally in the cerebral cortex in patients with OPCA.