Long-term effects of intracerebral bioactive substances

生长因子和激素对细胞的刺激常引起基因表达的改变，从而导致细胞反应的长期效应，这类反应已从基础和临床药理学的角度引起人们的关注。本研究从化学、分子生物学、电生理学和形态学等角度探讨了中枢神经系统中多种神经活性物质诱发细胞反应的机制，并取得了以下结果：(1)尼古丁呈剂量依赖性地抑制地塞米松诱导的红藻氨酸细胞毒作用。另一方面，单次注射雌激素在较低剂量下引起杏仁核神经元的细胞保护作用，在较高剂量下引起细胞毒性。(2)通过使用海马切片的电生理学研究，发现 ...更多信息 胆碱能调节参与苔藓纤维-CA 3突触突的长时程增强。(3)研究了酒精成瘾引起的细胞内GABA受体结构的变化。结果表明，酒精成瘾引起GABA_A和GABA_B受体的变化。据推测，这种抑制功能障碍与戒酒的发展有关。(4)从基因转导的角度研究了兴奋性氨基酸在脑内的长期作用机制。(5)用免疫组织化学方法检测背根节神经元和脊髓背角神经元GABA_A受体γ 1和γ 2亚单位及AMPA型谷氨酸受体Glu R1、2 mRNA的表达。(6)为了研究P物质对脑的作用，使用U-87 MG细胞研究了P物质受体表达的机制。(7)研究了戊四唑和红藻氨酸给药对海马中各种基因表达的影响。(8)c-fos mRNA的表达可被cenelifide抑制。(9)从大鼠脑中纯化激酶IV。这种激酶被发现是一种多功能的蛋白激酶，特异性分布在大脑中。少

It has been known that cell stimulation by growth factors and hormones often causes changes of gene expression which lead to long-term effects of cell response.Much attentions have been forcused on this kind of responses from viewpoints of basic and clinical pharmacology. The particularly important is that several kinds of protooncogenes are participated in chemical signal transduction as well as mechanism of drug addiction.In this study, mechanisms of cell responses evoked by various neuroactive substances in the central nervous system were investigated from viewpoints of chemistry, molecular biology, electrophysiology and morphology and following results were obtained. (1) Nicotine inhibited dexamethasoneinduced kainic acid cytotoxcity dose-dependently. On the other hand, single injection of estrogen into rat caused cytoprotection of amygdala neurons at lower doses and cytotoxicity at higher doses. (2) By means of electrophsiologcal studies using hippocampal slices, it was found that … More cholinergic regulation is participated in long-term potentiation at mossy fiber-CA3 synapes. (3) Changes of intracellular GABA receptor structure due to alcoholic addiction was studied. As the results, alcoholic addiction caused changes of both GABA_A and GABA_B receptors. It was assumed that such disorders of suppressive function are connected to development of alcoholic abstinence. (4) Mechanism of long-term effects of excitatory amino acids in the brain was studied from viewpoints of gene transduction. (5) Expression of mRNA of gamma1 and gamma2 subunit of GABA_A receptors and AMPA type glutamic acid receptors, Glu R1, 2 were examined in the dorsal root ganglion neurons and spinal dorsal horn neurons. (6) To examine substance P's effect on the brain, mechanism of substance P receptor expression was examined using U-87 MG cells. (7) Effect of pentylentetrazole and kainic acid administration on various gene expression in the hippocampus was studied. (8) Expression of c-fos mRNA induced by cycolohexamide was inhibited by cenelifide. (9) Kinase IV was purfied from rat brain. This kinase was found to be a multifunctional protein kinase specifically distributed in the brain. Less