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

（1）辅酶如吡咯喹啉醌、硫辛酸等，具有促进神经生长因子合成的作用，但不引起细胞毒性。特别是吡咯喹啉醌对小鼠星形胶质细胞有较强的促进NGF合成的活性，而硫辛酸对BALB c/3 T3细胞有较强的促进作用。（2）6-（4-羟丁基）-2，3，5-三甲基-1，4-苯醌（TMQ）刺激星形胶质细胞合成NGF。该化合物对基底前脑损伤大鼠（一种健忘症动物模型）的记忆和胆碱乙酰转移酶（CAT）活性显示出改善作用。TMQ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顶叶大脑皮层中降低的CAT活性，而且还增加了海马中的NGF含量和CAT活性。（3）用本系统测定的人血清、脑螺旋液及脑组织（海马和顶叶皮质）中的NGF水平与正常对照组无显著差异。 ...更多信息 正常人和老年痴呆症患者。(4)In烷基儿茶酚对NGF合成的刺激作用，既不是PKC依赖性途径，也不是cAMP依赖性途径。（5）白细胞介素（IL）-2对培养的18日龄大鼠海马神经元突起生长有促进作用。IL-2还支持培养的皮质、纹状体和隔神经元的存活。这些结果表明IL-2对多种神经元具有存活促进作用。（6）IL-4和IL-5可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对星形胶质细胞分泌NGF的量无明显影响。逆转录-聚合酶链反应（RT-PCR）方法显示，IL-4和IL-5在星形胶质细胞中的NGFmRNA水平显着增加。IL-4和IL-5的作用在静止的星形胶质细胞中比在生长的细胞中大。（7）黑质内注射6-羟多巴胺（6-OHDA）使去多巴胺能神经元的皮层和海马中的NGF含量增加，这两个区域都由胆碱能神经元支配。在病变后0.5-28天的观察期内持续增加。神经生长因子含量变化的时间过程与胆碱能神经元失神经支配的时间过程有很大不同。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