Alcohol Research Unit, Department of Biochemistry, The University of Queensland, St. Lucia, Qld. 4072, Australia; and Griffith University, School of Science, Nathan, Qld. 4111, Australia.
Mol Cell Neurosci. 1993 Dec;4(6):485-91. doi: 10.1006/mcne.1993.1060.
The temporal and spatial expression of three immediate early genes was investigated at the level of both mRNA and protein in the brains of rats undergoing ethanol withdrawal. Animals were made dependent by chronic vapor inhalation. All animals showed behavioral signs of withdrawal between 8 and 17 h after removal from ethanol vapor. A large, transient increase in the expression of whole brain c-fos, c-jun, and zif/268 mRNA was observed 12 h after withdrawal, and expression of their protein products was detected 15 to 24 h after withdrawal. Spatial variation in the expression of each protein was detected. All three proteins were present in the cerebral cortex, the olfactory bulb, the inferior colliculus, the granular cell layer of the cerebellum, and in the brain stem, but only C-JUN and ZIF/268 were detected in the hippocampus of animals undergoing withdrawal without overt seizures. C-FOS was detected in the hippocampus only in animals with overt seizures. These data reveal a complex pattern of immediate early gene expression during ethanol withdrawal, which may be associated with changes in neuronal plasticity and/or cell repair.
本研究采用原位杂交和免疫组织化学方法，观察了三种即刻早期基因（c-fos、c-jun 和 zif/268）在乙醇戒断大鼠脑内的时空表达。动物通过慢性蒸气吸入建立乙醇依赖模型。所有动物在停止吸入乙醇后 8-17 小时出现戒断症状。结果显示，在戒断后 12 小时，整个大脑的 c-fos、c-jun 和 zif/268mRNA 表达水平显著增加，15-24 小时后其蛋白产物表达水平增加。每种蛋白的表达在空间上均有差异。c-fos、c-jun 和 zif/268 在大脑皮质、嗅球、下丘、小脑颗粒细胞层和脑干中均有表达，但只有 c-jun 和 zif/268 在未出现明显癫痫发作的戒断动物的海马中被检测到。只有在出现明显癫痫发作的动物的海马中检测到 c-fos。这些数据揭示了乙醇戒断过程中即刻早期基因表达的复杂模式，这可能与神经元可塑性和/或细胞修复的变化有关。
