Dodd P R
Clinical Research Laboratory, Royal Brisbane Hospital Foundation, Bancroft Centre, Australia.
Metab Brain Dis. 1995 Mar;10(1):93-104. doi: 10.1007/BF01991786.
Synaptic plasma membranes were prepared from superior frontal gyrus and motor cortex obtained at autopsy from 17 chronic alcoholics not differentiated on thiamine status, of whom 8 had pathologically confirmed cirrhosis of the liver, and 10 controls. Three of the cirrhotic alcoholic cases were female, as was one control. Cases were closely matched for age at death and post-mortem delay. The affinity of "central-type" benzodiazepine sites for [3H]diazepam tended to be lower in both brain regions of both groups of alcoholics of cf controls, but the reverse was true for [3H]flunitrazepam, especially in cirrhotic cases. [3H]Diazepam affinity was invariant across all males and the female control, but lower in the female cirrhotic alcoholics. Affinity for [3H]flunitrazepam tended to be the reverse of that for [3H]diazepam. [3H]Diazepam Bmax was markedly lower in female cirrhotic alcoholics, especially in superior frontal gyrus, whereas this region showed a much higher Bmax in the female control case. A small regional difference in [3H]flunitrazepam Bmax was the reverse of that for [3H]diazepam Bmax and was seen in all groups. GABA-mediated neurotransmission may be selectively altered in a pathologically abnormal region of cerebral cortex in cirrhotic alcoholics, and the sexes may show differing susceptibilities to change.
突触质膜取自17例慢性酒精中毒者尸检时获得的额上回和运动皮层,这些患者未按硫胺素状态区分,其中8例经病理证实有肝硬化,另有10例为对照。肝硬化酒精中毒病例中有3例为女性,对照中有1例为女性。病例在死亡年龄和死后延迟方面进行了密切匹配。与对照组相比,两组酒精中毒者的两个脑区中,“中枢型”苯二氮䓬位点对[3H]地西泮的亲和力均趋于降低,但[3H]氟硝西泮的情况则相反,尤其是在肝硬化病例中。[3H]地西泮的亲和力在所有男性和女性对照中无变化,但在女性肝硬化酒精中毒者中较低。对[3H]氟硝西泮的亲和力趋势与[3H]地西泮相反。女性肝硬化酒精中毒者中[3H]地西泮的最大结合容量(Bmax)明显较低,尤其是在额上回,而在女性对照病例中该区域的Bmax则高得多。[3H]氟硝西泮Bmax的小区域差异与[3H]地西泮Bmax相反,且在所有组中均可见。肝硬化酒精中毒者大脑皮层病理异常区域的GABA介导的神经传递可能会被选择性改变,且不同性别对这种变化的易感性可能不同。