Studies on the molecular biology of the relationship between neurotrophin which functions to central nervous system (CNS) and Alzheimer's disease (AD)

(1)发现吡咯喹啉醌、硫辛酸等辅酶对NGF合成有刺激作用，但不产生细胞毒性。特别是吡咯喹啉醌在小鼠星形胶质细胞中表现出强烈的促进NGF合成的活性，而硫辛酸对BALB c/3T3细胞有强烈的影响。(2)6-（4-羟基丁基）-2,3,5-三甲基-1,4-苯醌（TMQ）刺激星形胶质细胞NGF合成。该化合物对基底前脑损伤大鼠的记忆和胆碱乙酰转移酶（CAT）活性有改善作用。TMQ可改善水迷宫和被动回避池中的健忘症。该化合物不仅恢复了大脑顶叶皮层中减少的CAT活性，还增加了海马中NGF含量和CAT活性。(3)应用我们的人NGF酶免疫测定系统测定了正常人和阿尔茨海默病患者的血清、脑螺旋液和大脑（海马和顶叶皮质）中的NGF水平。(4)烷基儿茶酚对NGF合成的刺激作用中，pkc依赖途径和camp依赖途径均不占主导地位。(5)白细胞介素(IL)-2支持培养的18日龄大鼠海马神经元的服务和增强的神经突延伸。IL-2也支持皮层、纹状体和间隔神经元的存活。这些结果表明，IL-2对多种神经元具有促进存活的作用。(6)IL-4和IL-5显著增加小鼠星形胶质细胞分泌NGF的量，而IL-2、IL-3和IL-6无显著影响。逆转录聚合酶链反应（RT-PCR）结果显示，星形胶质细胞中IL-4和IL-5的NGFmRNA水平明显升高。IL-4和IL-5在静止星形胶质细胞中的作用大于在生长细胞中的作用。(7)黑质内注射6-羟多巴胺（6-OHDA）使脱胺能神经元去神经化，增加了胆碱能神经元支配的皮层和海马的NGF含量。在病变后0.5-28天的观察期内，这种增加仍在继续。神经生长因子含量变化的时间过程与胆碱能神经元去神经的变化有较大差异。少

(1)The coenzymes such as pyrroloquinoline quinone, lipoic acid, found to have the stimulatory effect of NGF synthesis without causing cytotoxicity. Especially, pyrroloquinoline quinone showed strong activity of pormoting NGF synthesis in mouse astrocytes, whereas lipoic acid has the stong effect on BALB c/3T3 cells.(2)6-(4-Hydroxybuty1)-2,3,5-trimethy1-1,4-benzoquinone (TMQ) stimulated NGF synthesis in astrocytes. The compound showeds improving effects on memory and choline acetyltransferase (CAT) activity in basal forebrain-lesioned rats, an amnesia animal model. TMQ ameliorated amnesia in the water maze and passive avoidance tanks. This compound not only restored the reduced CAT activity in the parietal cerebral cortex, but also increased NGF content and CAT activity in the hippocampus.(3)The NGF level using our enzyme immunoassay system for human NGF were found to be no difference in NGF level in serum, brain-spiral fliud, or brain (hippocampus and parietal cortex) obatained from no … More rmal people and patients with Alzheimer's disease.(4)In the stimulatory effect of alkylcatechols on NGF synthesis, neither PKC-dependent pathway nor cAMP-dependent pathway was dominant.(5)Interleukin (IL)-2 supported the servival and enhanced neurite extention of cultured hippocampal neurons prepared from embryonic 18-day-old rats. IL-2 also supported the survival of cultured cortical, striatal, and septal ieurons. These results indicate that IL-2 has a survival-promoting effect on a wide variety of neurons.(6)IL-4 and IL-5 singifiantly increased the amounts of NGF secreted by mouse astrocytes, whereas IL-2, IL-3, and IL-6 had no significant effect. IL-4 and IL-5 showed marked increases in NGFmRNA levels in astrocytes as demonstrated by the reverse transcription-polymerase chain reaction (RT-PCR) method. The effect of IL-4 and IL-5 was greater in quiescent astrocytes than in growing cells.(7)Denervation of depaminergic neurons by intra nigra injection of 6-hydroxydopamine (6-OHDA) increased NGF content in the cortex and hippocampus, both of which are innervated by cholinergic neurons. The increase continued during an observation period of 0.5-28 days after the lesion. The time course of changes in NGF content was quite different from that of cholinergic neuron denervation. Less