Development of acute autoimmune encephalomyelitis in mice: Factors regulating the effector phase of the disease

The development of acute experimental autoimmune encephalomyelitis (EAE) in mice is potentiated by the use of Bordetella pertussis vaccine as an adjuvant. Histamine sensitizing factor (HSF) extracted from B. pertussis is the active adjuvant agent and causes a mild increase in cerebrovascular permeability. During the development of EAE, there is an additional increase in vascular permeability of the brain and spinal cord. The adjuvant action of B. pertussis HSF does not appear to mimic a generalized beta-adrenergic blockade, since the course of EAE is not potentiated by adrenalectomy. The cerebrovascular permeability changes observed in EAE are probably mediated by vasoactive amines, since the expression of EAE can be blocked by vasoactive amine antagonists.     

海洛因成瘾复吸大鼠脑组织超微结构和部分神经递质的变化

目的：建立海洛因成瘾、脱毒，复成瘾、脱毒，再成瘾、脱毒3个阶段大白鼠模型，了解海洛因致各阶段大白鼠脑损害的动态趋势。方法：电镜下观察脑超微结构变化，荧光分光度法测定脑NA、DA、5-HT等神经递质的含量。结果：3个阶段大鼠脑内多部位神经元胞体、轴突、树突都出现变性、凋亡、胀亡等超微病理结构改变，神经胶质细胞、神经毯也出现相应的超微病理结构改变，而且随复吸次数增多而病变加重。脑NA、DA、5-HT、含量升高，而且随复吸次数增多而升高。结论：大白鼠脑组织出现广泛性超微病理结构改变，随复吸次数增多而病变加重，脑神经递质含量也随复吸次数增多而升高。     

Quantitative distribution of rat brain monoamine oxidase A by [14C]clorgyline autoradiography

The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [¹⁴C]clorgyline in normal, conscious rat brain. [¹⁴C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [¹⁴C]methyliodide. Sixty minutes after [¹⁴C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus.     

Autonomic Correlates of Sensation Seeking and Monoamine Oxidase Activity: Using Confirmatory Factor Analysis on Psychophysiological Data

A negative relationship between platelet monoamine oxidase (MAO) activity and Sensation Seeking (SS) has been reported in several studies. This study evaluates the possible contribution of autonomic nervous system (ANS) activity to this relationship. Additionally, confirmatory factor analysis was used to create models of ANS concepts from a larger number of psychophysiological variables. Skin conductance (SC) and heart rate (HR) were recorded from 46 men and 49 women during a two-session protocol that included rest periods, a balloon stress, a series of tones, and two tasks: two-flash threshold and tachistoscopic recognition. Results showed that the best-fitting models for both rest and task periods included concepts of SC base levels (“arousal”), SC lability, and HR, and were quite similar for men and women. MAO activity correlated positively with SC concepts, most strongly for women. Women showed negative relationships between sensation seeking and both SC arousal and HR concepts. In contrast, men showed evidence of positive relationships between SC concepts and an active life style. The sex differences and response specificity in these relationships make it unlikely that ANS activity mediates the negative MAO-SS relationship.     

糖尿病大鼠视网膜基因表达谱差异的初步分析

目的 建立大鼠正常视网膜和糖尿病8周视网膜基因表达谱，比较两者差异，初步分析糖尿病视网膜病变的相关基因。方法 通过限制片段差异显示 PCR（ restriction fragments differential display-PCR，RFDD-PCR）获得正常大鼠视网膜及8周糖尿病大鼠视网膜组织转录组片段。应用Fraent Analysis等软件，对差异片段进行生物信息学分析，初步确定糖尿病视网膜病变相关基因／表达序列标签（ expression sequence tag, Ksr）。结果 获得有意义的片段共3639个，有差异的片段840个，占表达数的23．08％。其中包括5个视觉传导相关基因，13个兴奋性神经递质受体基因和3个抑制性神经递质受体基因。糖尿病8周大鼠视网膜Rhodopsin kinase,β-arrestin,Phosducin, rod photoreceptor cGMP-gated channel 和 Rpe65的表达下调，离子型谷氨酸受体iGluR1-4下调，代谢性谷氨酸受体及γ-氨基丁酸受体各亚型则普遍上调，而甘氨酸受体表达无变化。结论 糖尿病8周大鼠神经视网膜已受到累及，其基因表达模式的改变，可能与糖尿病早期视功能损害有关。     

Effect of cyclic GABA derivative TZ-146 on the content of neurotransmitters in rat brain stem

The effect of cyclic GABA derivative TZ-146 on the content of catecholamines, serotonin, their metabolites, and neurotransmitter amino acids in rat hypothalamus and brain stem was studied by high-performance liquid chromatography with electrochemical detection. Opposite changes in the content of homovanillic acid, aspartate, glutamate, and glycine in the examined structures were accompanied by inhibition of dopamine metabolism. Possible participation of cerebral glutamatergic system in the effect of TZ-146 is discussed. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 5, pp. 544–546, May, 2000     

Potentiation by deprenyl of the autoreceptor-mediated inhibition of [3H]-5-hydroxytryptamine release by 5-methoxytryptamine

Summary The 5-hydroxytryptamine (5HT) receptor agonist, 5-methoxytryptamine, inhibited in a concentration-dependent manner the electrically-evoked release of ³H-5HT from superfused rat hypothalamic slices, with an IC₅₀ of 560 nmol/l, without affecting the spontaneous outflow of radioactivity. In the presence of the selective monoamine oxidase B (MAO B) inhibitor, (–)-deprenyl (1 mol/l), the concentration-effect curve for 5-methoxytryptamine was shifted significantly to the left, and the IC₅₀ was decreased to 25 nmol/l. Under the same experimental conditions, the potency of the 5HT receptor agonist lysergic acid diethylamide (LSD) at inhibiting the electrically-evoked release of ³H-5HT was the same in the presence as well as in the absence of (–)-deprenyl. The IC₅₀ values for LSD were 34 nmol/l in the absence of deprenyl, and 31 nmol/l in the presence of the MAO B inhibitor. It is concluded that deprenyl potentiates the inhibition by 5-methoxytryptamine of ³H-5HT release, by preventing its inactivation through MAO B. Since 5-methoxytryptamine may be present in the pineal gland of some species, the potent effects of this 5-HT receptor agonist on seretoninergic neutrotransmission may be of physiological relevance.     

Stereoselective inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by 4-dimethylamino-2,α-dimethylphenethylamine (FLA 336)

Summary The in vitro inhibition by amiflamine [FLA 336(+)] and related compounds of the activity of rat monoamine oxidase (MAO)-A and-B, rat semicarbazide sensitive amine oxidase (SSAO) and human platelet poor plasma benzylamine oxidase was studied. Amiflamine was an MAO-A selective inhibitor, but also inhibits SSAO with both a reversible (competitive, K _i=200 mol/l) and a small time-dependent component which was irreversible in nature. The optical isomer FLA 336(–) was ten times less potent towards MAO-A. However, this compound was much more potent an inhibitor of SSAO (competitive, K _i=4.6 mol/l). The amiflamine metabolites FLA 788(+) and FLA 668(+) inhibited SSAO, but only at concentrations considerably higher than required for MAO-A inhibition. Ex vivo experiments indicated that there was no significant irreversible inhibition of rat heart and lung SSAO after both single and repeated administration of amiflamine at doses up to 20 times higher than required for inhibition of MAO-A within central serotoninergic neurones.     

APP转基因小鼠脑内单胺类递质的变化

用HPLC－ECD法对APP695,751V717Ⅰ转基因模型小鼠大脑皮层神经递质进行检测,结果显示APP751转基因鼠大脑皮层中的5－HIAA一与对照组比较有显著性差异。APP695转基因鼠大脑上以层中DA和5－HT平均含量分别比对照鼠升高38.9％和45.8%。提示Aβ的形成可能影响了多巴胺系统和5－羟色胺系统。     

补肾活血、泻下及开窍活血方药对老龄大鼠脑缺血再灌注心肌损伤的作用

为研究益元活血丹和大黄及血栓心脉宁对老龄大鼠脑缺血再灌注心肌损伤防护作用的机制。将老龄大鼠分为对照组、模型组、尼莫地平组、益元活血丹大小剂量组、大黄组、血栓心脉宁组,观察LDH、CPK活性和NE、DA、E、ET、CGRP、NPY的含量的变化。模型组血清中CPK、LDH活性和血浆ET及脑组织NPY含量增高,交感-肾上腺系统兴奋增强。与模型组比较,大黄组血清LDH和CPK活性减低,益元活血丹大剂量组和血栓心脉宁组及大黄组血浆ET含量、大黄组和益元活血丹大剂量组脑组织NPY含量降低,益元活血丹小剂量组血浆中CGRP水平增高;用药各组交感-肾上腺系统兴奋减低。提示大黄和血栓心脉宁及益元活血丹对心肌损伤的保护作用可能与其抑制交感-肾上腺系统兴奋增强和调节CGRP与ET间的平衡失调有关。