大鼠帕金森病模型的建立及其评价

目前越来越多的神经科学家致力于帕金森病的研究 ,并且已经建立了几种不同的动物模型 (如小鼠、大鼠和猴子模型 )。其中 ,大鼠模型应用最为广泛。本文对几种常用的大鼠帕金森病模型造模方法进行了简要的概述和评价。     

大鼠帕金森森病模型的建立及其评价

目前越来越多的神经科学家致力于帕金森病的研究，并且已经建立了几种不同的动物模型（如小鼠、大鼠和猴子模型）。其中，大鼠模型应用最为广泛。本文对几种常用的大鼠帕金森病模型造模方法进行了简要的概述和评价。     

鱼藤酮帕金森病大鼠模型建立的研究

目的探讨鱼藤酮帕金森病大鼠模型的建立方法.方法采用背部皮下注射鱼藤酮,然后观察大鼠的行为学及黑质-纹状体的酪氨酸羟化酶免疫活性变化、海马病理学变化.结果经过1～8周观察,鱼藤酮处理大鼠出现明显的行为学、黑质-纹状体酪氨酸羟化酶免疫活性变化,海马无明显病理学变化,模型显示出帕金森病的典型特征.结论背部皮下注射鱼藤酮的方法可成功制作帕金森病大鼠模型.     

慢性左旋多巴治疗对帕金森病大鼠行为及基底节Fos表达的影响

目的:研究帕金森病大鼠左旋多巴诱导异动症模型的行为学特征及其基底节区神经元活性的变化.方法:帕金森病大鼠给予左旋多巴治疗28 d,观察其行为学,并用免疫组织化学方法观察纹状体、苍白球区Fos表达情况.结果:慢性左旋多巴治疗后,帕金森病大鼠出现异常不自主运动,包括刻板运动和增加的对侧旋转行为.急性左旋多巴治疗帕金森病大鼠损毁侧尾壳核和苍白球区Fos表达均增加,慢性左旋多巴治疗与急性治疗组比较损毁侧尾壳核区Fos明显减少,而苍白球区表达增加.结论:慢性间断性左旋多巴治疗诱导帕金森病大鼠异常不自主运动是帕金森病患者左旋多巴诱导异动症的啮齿类动物模型,纹状体苍白球神经元活性增强可能参与其发生机制.     

帕金森病大鼠苍白球神经元放电模式的分析

目的 探讨帕金森病(Parkinson's disease,PD)大鼠苍白球(globus pallidus,GP)神经元的放电模式,为研究帕金森病的病理生理过程提供实验依据.方法 大鼠30只,应用6-羟基多巴胺(6-hydroxydopamine,6-OHDA)建立PD大鼠模型(模型组),多种方法对模型进行评价.在立体定向仪引导下记录PD模型组及正常生理状态下大鼠(对照组,10只)GP神经元放电活动,并对其放电模式进行分析.结果 模型组大鼠中有13只行为学及病理学检测结果符合PD模型标准.电生理记录显示对照组大鼠GP神经元放电频率为6±2Hz,模型组大鼠GP神经元放电频率为21±3Hz,模型组大鼠的放电频率显著高于对照组(P＜0.05).对照组共记录到四种形式的放电模式,模型组记录到三种.对照组GP神经元簇发放电模式的比例为11%,而模型组GP神经元簇发放电模式的比例术后四周为59%,术后八周为61%,两者比较具有统计学意义(P＜0.05).结论 PD模型大鼠GP神经元较生理状态下放电频率明显增加,其放电模式也有明显变化,簇状放电模式比例增大.这可能在帕金森病的病理生理变化中具有重要作用.     

Syn Bax 与 Bcl-2在帕金森病模型大鼠结肠中的表达及意义

目的：检测Syn、Bax、Bcl-2蛋白在帕金森病大鼠模型结肠中的表达及意义,探讨帕金森病消化系统功能紊乱的可能机制。方法采用羟多巴胺（6-hydroxydopamine ,6-O HDA ）损毁大鼠中枢黑质多巴胺能神经元,诱导制备实验性帕金森病大鼠模型。应用免疫组化法S-P法检测Syn、Bax、Bcl-2在帕金森病模型大鼠及正常对照组大鼠结肠组织中的表达情况。结果造模成功后,用免疫组化法S-P法,发现帕金森模型大鼠结肠中的Syn和 Bax表达水平较对照组增加,而Bcl-2表达水平较对照组减少。结论帕金森大鼠结肠组织中的Syn及Bax表达增加,Bcl-2表达减少,为研究帕金森患者肠道功能紊乱的机制提供线索。     

Fas基因沉默对帕金森病大鼠脑纹状体多巴胺能神经元凋亡的影响及机制研究

目的 探讨脂肪酸合成酶(Fatty acid synthase,Fas)基因沉默对帕金森病大鼠脑纹状体多巴胺能神经元凋亡的影响及机制.方法 取40只大鼠,30只大鼠脑纹状体注射4μL 6-羟基多巴胺(6-Hydroxydopamine Hydrobromide,6-OHDA)建立帕金森病大鼠模型,剩余10只为假手术组,...     

吡贝地尔对帕金森病大鼠模型脑多巴胺转运体影响的自显影研究

目的 研究常用抗帕金森药多巴胺受体激动剂吡贝地尔(泰舒达)对脑多巴胺转运体的影响。方法立体定位右侧纹状体注射6-羟多巴胺制备偏侧帕金森病大鼠模型,模型成功后予吡贝地尔灌胃治疗[30 mg/(kg·d)]5周。分4组(正常组、帕金森病模型大鼠组、帕金森病模型大鼠经吡贝地尔治疗组、帕金森病模型大鼠未治疗组)行大鼠脑多巴胺转运体田99Tcm-TRODAT-1放射自显影。图像分析得到纹状体与小腑的平均光密度值,计算并比较各组左、右两侧脑多巴胺转运体的特异性放射性摄取比值(纹状体/小脑-1)的变化。结果 正常大鼠脑多巴胺转运体对99Tcm-TRODAT-1的特异性放射性摄取比值左、右两侧无显著性差异;成为帕金森病模型后,两侧比值较正常均降低,右侧(损毁侧)降低叫显。未治疗组帕金森病模型大鼠双侧比值均较刚成模型时明显升高;经吡贝地尔治疗后,双侧比值均较未治疗组显降低,右侧(损毁侧)降低更甚。结论 长期吡贝地尔(泰舒达)治疗可能会使帕金森病模型大鼠脑多巴胺转运体的数量减少。     

吡贝地尔对帕金森病模型大鼠脑多巴胺D2受体的影响

目的研究常用抗帕金森药多巴胺受体激动剂吡贝地尔对脑多巴胺D2受体的影响。方法立体定位右侧纹状体注射6-羟多巴胺制备偏侧帕金森病大鼠模型,模型成功后予吡贝地尔灌胃治疗[30mg/(kg·d)]5周。分4组(正常组、术后4周帕金森病模型大鼠组、术后9周帕金森病模型大鼠经吡贝地尔治疗组、术后9周帕金森病模型大鼠未治疗组)行125I-依匹必利(125I-epidepride)大鼠脑多巴胺D2受体放射自显影。图像分析得到纹状体与小脑的平均光密度值,计算并比较各组左、右两侧脑多巴胺D2受体的特异性放射性摄取比值(纹状体/小脑-1)的变化。结果正常大鼠脑多巴胺D2受体对依匹必利的特异性放射性摄取比值左、右两侧差异无统计学意义;成为帕金森病模型后,右侧(损毁侧)比值较正常稍升高,但差异无统计学意义;未治疗组帕金森病模型大鼠双侧比值较刚成模型时均明显降低,右侧(损毁侧)比值仍较左侧高;经吡贝地尔治疗后,双侧比值较未治疗组进一步降低,右侧(损毁侧)降低甚,比值较左侧低。结论长期吡贝地尔治疗可能会使帕金森病模型大鼠双侧脑多巴胺D2受体的数量减少,损毁侧减少为甚。     

氧自由基在帕金森病发病中作用的实验研究

目的 观察氧自由基在帕金森病发病中的作用。方法 大鼠分为3组：帕金森病组、假手术组、对照组。帕金森病大鼠模型采用6羟基多巴胺(6—OHDA)制作。采用生化、电镜方法观察铁离子、氧自由基浓度及黑质超微结构变化。结果 帕金森病组大鼠铁离子、氧自由基浓度及黑质损伤程度均高于对照组和假手术组。结论 氧自由基在帕金森病发病中起着重要作用。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.     

Summary of Legislation of 1933 of interest to the Department of Mental Hygiene

Psychiatric Quarterly -