Long-term effects of intracerebral bioactive substances

众所周知，生长因子和激素对细胞的刺激往往会引起基因表达的改变，从而导致细胞反应的长期效应，从基础药理学和临床药理学的角度对这种反应进行了大量的研究。尤其重要的是，多种原癌基因参与了化学信号转导和药物成瘾的机制。本研究从化学、分子生物学、电生理学和形态学的角度，对中枢神经系统中各种神经活性物质引起的细胞反应机制进行了研究，取得了以下结果。(1)尼古丁对地塞米松诱导的红藻氨酸细胞毒性具有剂量依赖性抑制作用。另一方面，单次注射雌激素对大鼠杏仁核神经元具有低剂量的细胞保护作用和高剂量的细胞毒性作用。(2)通过对海马脑片的电泳学研究，发现…更多的胆碱能调节参与苔藓纤维-CA3突触的长时程增强。(3)研究酒精成瘾对细胞内GABA受体结构的影响。结果表明，酒精成瘾可引起GABA_A和GABA_B受体的改变。据推测，这种抑制功能障碍与酒精戒断的发展有关。(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)在背根神经节神经元和脊髓背角神经元中检测到GABA_A受体的Gamma1和Gamma2亚单位和AMPA型谷氨酸受体Glu R1、2的mRNA表达。(6)用U-87 MG细胞研究P物质受体的表达机制，探讨P物质对脑的影响。(7)研究了戊四唑和红藻氨酸对大鼠海马区多种基因表达的影响。(8)西奈德可抑制环六亚胺诱导的c-fos基因表达。(9)从大鼠脑中提纯了Kinase IV。这种激酶被发现是一种专门分布在大脑中的多功能蛋白激酶。较少

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