Predictors of punding in Parkinson's disease: results from a questionnaire survey.

Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD.     

微囊化猪视网膜色素上皮细胞移植治疗帕金森病的实验研究(英文)

目的研究微囊化后的猪视网膜色素上皮细胞(retinal pigment epithelial,RPE)对帕金森病大鼠模型的移植疗效。方法原代培养RPE 并传代,高效液相色谱法测定培养液上清中多巴胺(dopamine, DA)和高香草酸(homovanillic acid, HVA)的含量,ELISA法检测脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)和胶质细胞源性神经营养因子(glial-derived neurotrophic factor, GDNF)的含量。用高压静电成囊装置制备海藻酸钠-多聚赖氨酸-海藻酸钠微囊化细胞。6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)毁损内侧前脑束 (medial fore-brain bundle,MFB)建立 SD 大鼠帕金森病模型。立体定向移植 RPE+ 微囊,检验旋转实验、免疫组化和脑内生化的变化。结果 RPE 培养上清液中DA、HVA、BDNF、GDNF 的含量稳定,微囊化后细胞长期存活,活性没有明显变化。6-OHDA毁损MFB建立大鼠帕金森病模型的成模率为83%。移植微囊化的RPE后有效率为33%。结论猪 RPE 体外培养生长旺盛,持续分泌 DA、BDNF 和 GNDF,微囊化不影响其分泌功能。RPE 移植对帕金森病大鼠有一定的治疗作用。     

Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.     

麻醉剂量羟甲芬太尼对大鼠脑内单胺递质及其代谢物含量的影响

麻醉剂量羟甲芬太尼对大鼠脑内单胺递质及其代谢物含量的影响金昔陆１唐琴梅金文桥周德和李桂芬池志强（中国科学院上海药物研究所，上海２０００３１）羟甲芬太尼（ｏｈｍｅｆｅｎｔａｎｙｌ，ＯＭＦ）是一种新的高选择性高亲和力μ阿片受体激动剂，在动物中能产生麻醉作...     

Transmitter Release Associated with Long-term Synaptic Depression in Rat Corticostriatal Slices

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.     

Pharmacological modulation of endogenous dopamine and DOPAC outflow from nucleus accumbens

The release of endogenous DA and DOPAC from nucleus accumbens slices were studied measuring net outflow of DA and DOPAC in the superfusate of static chambers, to analyze the correlation between DA and DOPAC outflows and identify which DA stores may serve as possible sources for DOPAC formation. Under resting conditions, or following stimulation with low (< 15 mM) KCl concentration, DOPAC outflow was greater than DA. When DA release was stimulated by higher (> 25 mM) KCl concentrations, DA outflow increased, proportionally more than DOPAC. In the virtual absence of Ca²⁺ in the Krebs solution DA outflow, induced by 25 mM KCl, was reduced to about 10%, while DOPAC outflow was only reduced to 45%. When the synthesis of DA was inhibited with -MPT, DA and DOPAC outflow were unchanged during the first stimulation period. During a second stimulation period, however, their outflow were significantly reduced. Nomifensine, a DA uptake inhibitor, increased the basal DA outflow by about 100%, but only blocked DOPAC basal outflow by about 25%. The 25 mM KCl stimulated DA outflow was not affected by Nomifensine, while the stimulated DOPAC outflow was reduced by about 50%. These results demonstrate that there is a weak correlation between the outflows of DA and DOPAC, suggesting a complex relationship between the mobilization of the different DA pools and DOPAC outflow. The formation of DOPAC from some of these pools, appear to be dependent on the stimulation levels and on the pharmacological manipulation of the tissue.     

Microstructure of the non-rapid eye movement sleep electroencephalogram in patients with newly diagnosed Parkinson's disease: effects of dopaminergic treatment.

We investigated non-rapid eye movement (non-REM) sleep in patients with newly diagnosed Parkinson's disease (PD) who had never previously received dopaminergic medication. There were no significant differences in the conventional sleep parameters between de novo patients with PD and a healthy control group, but the length of stage 1 sleep and the number of awakenings increased significantly upon administration of dopaminergic drugs. Analyzing the quantitative electroencephalogram (EEG), we observed a significant reduction in the low-delta frequency range and a nonsignificant increase in the sigma frequency range in de novo patients with PD. The dopaminergic medication also nonsignificantly reduced the low-delta and sigma frequencies, the latter to the level of the controls. Possible mechanisms that may account for the observed differences are discussed. It is suggested that Parkinson's disease as well as the application of dopaminergic drugs exerts a desynchronizing effect on the sleep EEG that is reflected in a disruption of sleep continuity.     

HIGH-LEVEL EXPRESSION OF RATD1A DOPAMINE RECEPTOR cDNA IN MOUSE FIBROBLASTLTK- CELLS BY n-BUTYRATE

1. In orefer to develop a simple, efficient system for the highlvel expression of dopamine recetors in eukaryotic cells, we have studied the effects of n-butyrate on the expression of rat D_1A dopamine receptor cDNA in mouse fibroblast LTK- cells as compared with those of n-butyrate on endogenous D₁ receptor levles in opossum kidney cells.
2. In the transfected LTK- cell mebranes with pRc/CMVD_1A receptor cDNA, a selective D₁ dopamine antagonist, [³H]-SCH 23390, exhibited a K_d of 0.9 ± 0.1 nmol/L and a B_max of 0.35 ± 0.05 pmol/mg protien (n = 5).
3. Addtion of n-butrate (2–10 mmol/L) to the culture medium for 48h dose-dependently increased the D_1A receptor level up to 1.5 ± 0.3 pmol/mg protien (n = 7), although the K_d values were not affected. The increase in receptor level was accompanined by an elevation of selective D₁ agoinist-induced adenyly cyclase activity.
4. In contrast, n-butyrate treatment (2–10 mmol/L) did not affect either endogenous D₁ receptor levels or fendoldopmainduced adenylyl cyclase activity in possum kidney cells.
5. These results sugges n-butyrate is a sueful tool for obtaining high-level expression of D_1A dopamine receptor cDNA in mouse fibroblast LTK- cells.     

羧基化多壁碳纳米管修饰电极伏安法测定多巴胺

目的 :研究用羧基化多壁碳纳米管修饰电极伏安法测定痕量多巴胺 (DA)的效果。方法 :采用涂布法制成羧基化多壁碳纳米管修饰电极 ;在pH =5 .4的KH2 PO4 Na2 HPO4缓冲溶液中 ,采用该修饰电极伏安法测定DA。结果 :该修饰电极对DA有着显著的电催化作用 ,与裸玻碳电极相比较 ,其灵敏度大大提高 ,在2 .0× 10 -7～ 6 .0× 10 -4mol/L浓度范围内 ,DA的氧化峰电流与浓度成良好的线性关系 ,检测限为 5 .0× 10 -8mol/L。将该修饰电极用于盐酸多巴胺针剂的测定 ,相对平均偏差为 1.4 % ,平均回收率为 99.2 %。结论 :该修饰电极响应快 ,灵敏度高 ,稳定性好 ,寿命长 ,适合于具有电活性生物分子的测定