ALCOHOL, BRAIN METABOLISM AND BENZODIAZEPINE RECEPTOR BINDING

死后神经病理研究表明，过度的慢性 摄入乙醇可减少额叶上区神经元的数量 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- 额叶皮质A/苯二氮(BDZ)受体可能减少 和海马体，但不在大脑皮层的其他区域。利用 用[11C]氟马西尼进行正电子发射断层扫描(PET)，我们建议 确定BDZ受体密度是否在 慢性酒精依赖者的额叶皮质 与年龄和性别相近的一组正常对照组进行比较 分配。PET与[18F]氟代脱氧葡萄糖的配伍 受试者，我们将检测局部大脑葡萄糖代谢率 (LCMRG)，并比较BDZ受体结合的分布与 LCMRG的分布格局。我们预计在慢性酒精依赖患者中会发现 患者BDZ受体密度下降， 大脑皮层额上区的LCMRG。我们将使用 神经心理测试也同样研究额叶功能。 患者，并预计会发现性能下降和 与BDZ受体和LCMRG减少的水平相关 额叶上皮质。 神经病理学研究还表明，长期过量摄入 乙醇可减少小鼠上蠕虫内神经元的数量 小脑，即使在没有小脑障碍症状的患者中也是如此 在生活中。慢性血吸虫病死后组织生化研究 酒精依赖受试者提示BDZ受体结合可能是 在小脑中减少。我们建议使用[11C]氟马西尼和 [18F]氟脱氧葡萄糖PET检测BDZ受体密度 临床有症状患者的LC-MRG表现 慢性酒精依赖的酒精性小脑变性(ACD) 无小脑变性证据且正常的患者 年龄和性别分布相近的受试者。为了检测到 任何由解剖连接引起的生化变化 大脑皮层和小脑，我们还建议研究患者 患有慢性小脑变性(主要为遗传性 橄榄桥小脑萎缩，OPCA)使用相同的PET探针 确定BDZ结合中的焦点扰动是否会降低LCMRG 局限于小脑前上段。我们期待着找到 减少了BDZ的结合，并减少了限制在酒精中的LCMRG- 无ACD依赖患者，BDZ结合量减少且减少 LCMRG广泛分布于小脑，但不局限于大脑皮层。 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.