STRESS AXIS, ACTIVATION, SITE SPECIFIC CNS NEURODEGENERATION AND ETHANOL

乙醇(ET)的消费改变了某些监管方面的 下丘脑-垂体-肾上腺轴(HPAA)。因为它的完整性 这一系统依赖于协调合成和分泌 下丘脑的特定调节物质(例如，促肾上腺皮质激素- 促肾上腺皮质激素释放激素(CRH)；加压素(AVP)；生物胺 腺体(例如，β-内啡肽；ACTH)和肾上腺(例如， 儿茶酚胺；糖皮质激素)水平，我们一直在评估 ET对HPAA各层级的影响。激活HPAA或 短期和长期服用ET都伴随着皮质醇增多症 和ET戒断综合征。酗酒者通常会出现一种伪装- 库欣综合征，约17%-40%的酗酒者 对地塞米松抑制试验的反应在第一周 禁欲。由于糖皮质激素升高的相对状态(慢性 连续性或慢性间歇性)可导致神经改变，甚至 细胞死亡，特别是在海马体中，进行性丧失 许多酗酒者的认知能力确实可能部分归因于 高皮质醇血症和随后不可逆转的神经损伤 海马体和中枢神经系统的其他区域。使用 大鼠胃内插管模型及短期(4天)间歇性造模 酒精注射，我们已经展示了特定部位的中枢神经系统 海马齿状回的神经变性， 内鼻孔皮质和梨状皮质。对政府的作用进行评估 谷氨酸能神经递质增加，钙摄取增加， 在观察到的神经退行性变中，糖皮质激素随着激素的增加而继续 和药物替代疗法。这个项目以前是 题为“应激轴、免疫系统衍生的细胞因子和乙醇”。

Consumption of ethanol (Et) alters certain regulatory aspects of the hypothalamic-pituitary-adrenal axis (HPAA). Because the integrity of this system depends on the coordinated synthesis and secretion of specific regulatory substances at the hypothalamic (e.g., corticotropin- releasing hormone (CRH); vasopressin (AVP); biogenic amines), pituitary- gland (e.g., beta-endorphin; ACTH) and adrenal gland (e.g., catecholamines; glucocorticoids) level, we have been evaluating the impact of Et at each level of the HPAA. Activation of the HPAA or hypercortisolism accompanies both short- and long-term consumption of Et and the Et withdrawal syndrome. Alcoholics often present with a pseudo- Cushing's syndrome in which some 17-40 percent of alcoholics do not respond to the dexamethasone suppression test during the first week of abstinence. Since a relative state of elevated glucocorticoids (chronic continuous or chronic intermittent) can lead to neural changes and even cell death, particularly in the hippocampus, the progressive loss of cognitive capacity in many alcoholics may indeed be due in part to hypercortisolemia and subsequent irreversible neural damage in the hippocampus and other areas of the central nervous system. Using an intragastric cannulated rodent model and short-term (4 days) intermittent alcohol administration, we have demonstrated site-specific CNS neurodegeneration in the dentate gyrus of the hippocampus, the entorherial cortex and the piriform cortex. Assessment of the role of increased glutamatergic neurotransmission, Ca++ uptake and levels of glucocorticoids in the observed neurodegeneration continues with hormonal and pharmacological replacement therapy. This project was formerly titled "Stress Axis, Immune System-Derived Cytokines and Ethanol."