Binienda Z, Scallet A C
Division of Neurotoxicology, Food and Drug Administration, Jefferson, AR 72079-9502.
Int J Dev Neurosci. 1994 Nov;12(7):605-10. doi: 10.1016/0736-5748(94)90012-4.
Metabolic stressors such as hyperthermia, seizures and ischemic hypoxia result in the induction of c-fos and heat-shock proteins (HSP) in affected brain cells of the adult rodent, especially within the hippocampal region, which normally has high metabolic demands. Here we ligated the uterine vessels of gestational day (GD) 21 rat pups to produce ischemic hypoxia. We confirmed that HSP-72 protein, as previously reported, was activated in the perinatal rat pup, especially in the hippocampal CA3 region. However, the capability of hippocampal cells to produce c-fos protein following drug-induced seizures has been reported to develop only after postnatal day 13. Here, ischemic hypoxia caused CA1 hippocampal cells to produce immunohistochemically detectable c-fos protein in GD-21 rats. These results seem to contradict the previous reports of no c-fos induction in rats this young by demonstrating a functional c-fos translational mechanism by GD-21. However, seizure vs ischemic hypoxia-induced c-fos expression may involve several different pre-translational pathways. A delayed development of a receptor, second messenger, or genomic element for regulating c-fos transcription remain as possible explanations for the late maturity of responsivity to seizures.
诸如高热、癫痫发作和缺血性缺氧等代谢应激源会导致成年啮齿动物受影响的脑细胞中c-fos和热休克蛋白（HSP）的诱导，特别是在通常具有高代谢需求的海马区域。在此，我们结扎了妊娠第21天（GD21）大鼠幼崽的子宫血管以产生缺血性缺氧。我们证实，如先前报道的那样，HSP-72蛋白在围产期大鼠幼崽中被激活，尤其是在海马CA3区域。然而，据报道，药物诱导的癫痫发作后海马细胞产生c-fos蛋白的能力仅在出生后第13天之后才发育。在此，缺血性缺氧导致GD21大鼠海马CA1细胞产生免疫组化可检测到的c-fos蛋白。这些结果似乎与之前关于如此年幼的大鼠中无c-fos诱导的报道相矛盾，因为在GD21时证明了一种功能性的c-fos翻译机制。然而，癫痫发作与缺血性缺氧诱导的c-fos表达可能涉及几种不同的翻译前途径。调节c-fos转录的受体、第二信使或基因组元件的延迟发育仍然是对癫痫发作反应性成熟较晚的可能解释。
