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28d，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。     

MK-801对左旋多巴诱导异动症大鼠模型基底节区神经元活性的影响

目的:研究NMDA(N-methyl-D-aspartate)受体拮抗剂MK-801对左旋多巴诱导的帕金森病大鼠异常不自主运动行为学及其基底节区Fos表达的影响,探讨谷氨酸对长期左旋多巴治疗后帕金森病大鼠基底节输出通路活性改变的影响。方法:帕金森病大鼠给予左旋多巴治疗28d,第29d左旋多巴治疗前15min腹腔注射MK-801一次。观察其行为学变化,并用免疫组织化学方法观察尾壳核和苍白球Fos表达情况。结果:长期间断左旋多巴治疗后,帕金森病大鼠出现刻板运动和进行性增加的对侧旋转等行为学改变。提前用MK-801抑制了其刻板动作,而增加了对侧旋转行为。与左旋多巴治疗组比较,MK-80l治疗组损毁侧尾壳核区Fos表达明显增多而苍白球区Fos表达明显减少。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和旋转期缩短是帕金森病患者左旋多巴诱导异动症和疗效减退的啮齿类动物模型,谷氨酸在其发生机制中发挥重要作用,NMDA受体拮抗剂可能通过逆转直接通路的活动而抑制异动症和疗效减退的发生。     

经颅重复性磁刺激后大鼠纹状体FosB蛋白的表达

观察经颅重复性低频磁刺激（rTMS)对大鼠纹状体FosB蛋白表达的影响。6－OHDA单侧损毁纹状体边缘区,磁刺激器给予大鼠头部1Hz,100mT的重复性刺激,14d后用免疫组织化学ABC法检测纹状体FosB免疫阳性产物。rTMS后能够引起大鼠纹状体区域明显的FosB蛋白表达,这种表达广泛分布于尾壳核及苍白球,尤以腹侧纹状体及尾侧的壳核明显。6－OHDA损毁后予以rTMS,损毁侧Fos蛋白表达未出现减少,且尾壳核的背外侧部表达明显上调。对照组动物仅损毁侧有少量的FosB表达外,纹状体内未见FosB阳性标记。经颅重复性低频磁刺激能够激活纹状体内神经元,推测rTMS可能在增加多巴胺释放的同时,又能够激活多巴胺受体的活性,故在帕金森病等的治疗上有一定的意义。     

地佐环平对左旋多巴引起帕金森病大鼠行为和基底节Fos表达的影响

左旋多巴诱导的异动症 (levodopa induceddyskinesia,LID)是长期左旋多巴治疗帕金森病 (Parkinson’sdisease,PD)的不良反应。皮质纹状体谷氨酸神经元活性增强可能参与其发生机制。鉴于近年来对长期左旋多巴治疗诱导的PD大鼠异常不自主运动 (AIM )与人类LID相似性的认识 ,我们研究了谷氨酸受体拮抗剂地佐环平 (MK 80 1)对左旋多巴诱导的AIM大鼠行为学和基底节区神经元活性的影响。材料和方法 :健康SD雄性大鼠 (2 0 0～ 2 5 0 g) ,采用 6 羟基多巴胺 (6 OHDA)立体定向注射术制备PD大鼠模型。每天 2次给予PD大鼠左旋多巴 (10mg/…     

左旋多巴诱发异动症大鼠模型基底节区谷氨酸脱羧酶表达的研究

目的 研究左旋多巴诱发异动症(LID)大鼠模型尾壳核、苍白球及黑质网状部谷氨酸脱羧酶(GAD)表达的变化。方法用免疫组织化学方法观测大鼠尾壳核、苍白球及黑质网状部GAD的表达变化，用辣根过氧化物酶(HRP)逆行示踪与免疫组织化学相结合的双重反应技术观测GAD的细胞分布状况。结果 LID大鼠较正常及非LID大鼠尾壳核区GAD明显增加，尤其在尾壳核外侧区增加更明显，且主要分布在纹状体黑质神经元内，苍白球区GAD明显增加，而黑质网状部GAD减少。结论 大鼠基底节区GAD表达变化与LID的发生有关，直接通路活动异常及基底节环路功能异常参与大鼠LID的发生。     

多巴胺D1和谷氨酸NMDA受体参与调控异动症大鼠纹状体△FosB蛋白的表达

目的研究多巴胺D1和D2受体以及谷氨酸NMDA受体对△FosB蛋白表达水平的影响,由此探讨它们在左旋多巴诱导的异动症(Levodopa-induced Dyskinesia,LID)发病机制中的作用。方法对单侧黑质纹状体6-羟多巴胺(6-OHDA)损毁致帕金森病(PD)大鼠给予左旋多巴治疗28d制作LID模型,将大鼠分为7组:正常对照组、PD组、LID组、SCH23390治疗组、MK-801治疗组、raclopride治疗组和非LID组,分别观察各组行为学改变并进行异常不自主运动(abnormal involuntary movement,AI M)评分,用免疫组化和免疫印迹方法测定各组△FosB蛋白表达水平。结果多巴胺D1受体阻断剂SCH23390和谷氨酸NMDA受体阻断剂MK-801明显减轻LID大鼠行为学异常,而多巴胺D2受体阻断剂raclopride对异常不自主运动无明显影响;LID大鼠损毁侧纹状体△FosB蛋白表达较PD大鼠和非LID大鼠明显增加;与LID大鼠相比,MK-801和SCH23390均使△FosB蛋白表达显著下降,而raclopride没有这种效应;各组大鼠健侧纹状体△FosB蛋白表达水平没有显著差异。结论多巴胺D1受体和谷氨酸NMDA受体均通过参与调控纹状体△FosB蛋白的表达而影响大鼠LID的发生。     

β-arrestin1参与MK-801治疗帕金森病异动症的研究

目的 探讨MK-801缓解帕金森病(PD)异动症的治疗机制。方法 建立PD运动并发症大鼠模型,25只大鼠随机分为3组：异动症(LID)组10只、MK-801处理组10只、PD组5只,另设假手术组5只为对照组。观察MK-801治疗左旋多巴诱导的异动症大鼠模型的行为学变化,并采用免疫组织化学方法和Western blot印迹法检测大鼠纹状体区β-arrestin1的表达情况。结果 MK-801处理后,LID大鼠模型异常不自主运动评分降低和剂峰旋转行为减弱。免疫组织化学结果显示LID组损伤侧β-arrestin1阳性细胞指数[(2.95±0.44) ×104]明显较未损伤侧[(3.78 ±0.37)×104]降低,差异有统计学意义(t =5.415,P＜0.05)。Western blot结果显示,PD模型组损毁侧与未损毁侧纹状体区β-arrestin1含量比值为81.02％ ±2.23％;LID组(64.88％±3.10％)蛋白表达量进一步减少,与PD组比较,差异有统计学意义(t=9.47,P＜0.01);而MK-801组蛋白表达量增高至89.26％±1.90％,与LID组相比,差异有统计学意义(t=14.82,P＜0.01)。结论 MK-801能缓解LID大鼠的行为学变化,其机制可能与β-arrestin1表达增多抑制了谷氨酸受体的过度活化有关。     

左旋多巴诱发异动症大鼠模型纹状体神经元可塑性的研究

目的 研究左旋多巴诱发异动症(LID)大鼠模型纹状体区FosB和特异性神经肽基因表达的变化，探讨LID时纹状体神经元的可塑性。方法 分别用免疫组织化学方法和逆转录聚合酶链反应技术(RT-PCR)检测大鼠纹状体区FosB和前脑啡肽原(PPE)及前强啡肽原(PDyn)基因的表达情况。用辣根过氧化物酶(HRP)逆行示踪与免疫组织化学相结合的双重反应技术观测FosB的细胞分布状况。结果 帕金森病(PD)大鼠较正常大鼠损毁侧纹状体PPE mRNA表达明显增多而PDyn mRNA表达减少。LID大鼠较PD大鼠PPE mRNA无明显增多，但PDyn mRNA显著性增多。LID大鼠损毁侧纹状体区FosB阳性神经元明显增多，并且主要分布于纹状体黑质神经元内。结论 纹状体黑质神经元内即早基因FosB及其下游靶基因强啡肽的表达异常与大鼠LID的发生有关，表明LID的发生与直接通路的活动异常密切相关。     

大麻素CB1受体在左旋多巴诱导的异动症大鼠基底节的表达研究

目的观察大麻素CB1受体在长期左旋多巴治疗诱导的异动症(LID)大鼠模型基底节表达的特点,探讨LID与CB1受体表达变化的关系。方法帕金森病(PD)模型大鼠接受左旋多巴腹腔注射21 d,建立LID大鼠模型。采用免疫组化和Western Blot方法检测基底节不同部位CB1受体表达。结果经左旋多巴治疗的PD大鼠出现类似人类LID的行为学表现。免疫组化结果显示LID组纹状体CB1受体损伤侧与未损侧的累积吸光度(IOD)比值下降,而苍白球和黑质网状部该比值升高(均P0.01);Western blot检测结果与免疫组化显示了相同变化趋势,LID组纹状体CB1受体损伤侧/未损侧条带密度比值降低(P0.01)。结论长期左旋多巴治疗可引起基底节纹状体CB1受体表达下调,这种改变可能与LID的发生发展有关。     

FosB/△FosB在左旋多巴治疗帕金森病大鼠诱发异动症中的表达与作用

目的探讨FosB/△FosB在左旋多巴治疗帕金森病大鼠诱发异动症中的表达与作用。方法左侧内侧前脑束(MFB)立体定位注射6-羟多巴胺(6-OHDA)制备偏侧帕金森病(PD)大鼠模型,筛选出完全毁损和部分毁损的偏侧PD大鼠模型。完全毁损与部分毁损左旋多巴治疗组PD大鼠分别给予左旋多巴治疗,完全毁损生理盐水治疗组PD大鼠给予生理盐水治疗,假手术大鼠为对照组。每组实验终点,旋转行为评估药物疗效,免疫组织化学技术检测纹状体区FosB/△FosB表达水平。结果随左旋多巴治疗时间的延长,动物旋转圈数逐渐缩短(P<0.01),异动症(AIM)评分逐渐升高(P<0.01),部分毁损PD大鼠的AIM评分低于完全毁损者(P<0.01),毁损侧纹状体区FosB/△FosB阳性细胞数、平均光密度值逐渐增高(分别P<0.01),完全毁损组高于部分毁损者(P<0.01)。生理盐水治疗的PD大鼠纹状体区FosB/△FosB阳性细胞数、平均光密度值无明显变化(P>0.05)。结论纹状体区FosB/△FosB表达水平的改变可能参与了左旋多巴诱发异动症的产生。     

Mechanisms of the suppression of the nociceptive reflex of the opening of the mouth during stimulation of the structures of the limbic brain

The comparative effectiveness of the inhibitory influence of tetanic stimulation of hypothalamus, amygdala and limbic cortex on EMG-response of m. digastricus evoked by electrical stimulation of tooth pulp nociceptive afferents was studied in cats anesthetized with a mixture of chloralose and nembutal. It was found that inhibition of the EMG-component of the jaw-opening reflex is most pronounced in case of stimulation of medial and lateral region of the hypothalamus, the inhibitory effect of central and medial nuclei of the amygdala is less pronounced and the effect of the limbic cortex is the weakest. It was shown that the mechanism of the antinociceptive effect of tetanic stimulation of the hypothalamus is not related to the concomitant increase of the blood pressure. After stabilization of the blood pressure the suppressive effect of the hypothalamus remains without changes, that points out to a direct, primary, not baro-afferent mechanism of the inhibition of the activity of nociceptive neurons of the trigeminal sensory nuclei. Noradrenaline, injected intravenously, induced a large increase of the blood pressure accompanied by a pronounced inhibition of the pain reflex. Angiotensin causes the same degree of blood pressure elevation without changes in the amplitude of the EMG-response of the pain reflex. Hypothalamic and noradrenergic mechanisms for control of pain sensitivity are discussed.     

药物治疗与合并认知行为治疗对强迫症疗效的比较

目的探讨认知行为心理治疗(CBT)在强迫症(OCD)患者各亚型治疗中的有效性和规律性。方法本研究为临床对照研究。符合入组标准的强迫症患者按患者自愿原则分为两组,治疗观察3、6、12个月。疗效评定分别运用Yale-Brown强迫量表,自拟的自评好转程度量表和临床疗效评定。结果认知行为心理治疗合并药物治疗组31例,临床有效率70.9%,其中治愈率1.8%。单纯药物治疗组24例,临床有效率33.3%。Yale-Brown强迫量表和自评量表得分在6个月和12个月两组有显著差异(P<0.05)。其中强迫症亚型(怕脏型、反复检查型和反复担心型)的疗效比较,怕脏型在治疗3个月末两组间自评量表评分有显著性差异(P<0.05);反复担心型在治疗6个月末两组间Yale-Brown强迫量表总分有显著性差异(P<0.05);反复检查型两组间无统计学差异。结论认知行为心理治疗合并药物治疗强迫症的疗效明显优于单纯药物治疗。强迫症的亚型在治疗中的有效性次序为:反复担心型>怕脏型>反复检查型。     

Characteristics of the sympathetic innervation of the nictitating membrane and of the vasculature of the nose and tongue of the cat

Summary Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membrane, were recorded on stimulation of the cervical sympathetic or internal carotid nerves.Preganglionic sympathetic nerve fibres which elicited a membrane response possessed a lower threshold than those which evoked nasal vasoconstriction, while the latter displayed a lower threshold than fibres which evoked tongue vasoconstriction. The sympathetic vasodilator fibres to the tongue, whose activity was revealed after-receptor blockade, had a similar threshold to the vasoconstrictor fibres.Membrane contraction, nasal vasoconstriction and occasionally tongue vasoconstriction could be evoked by stimulating the internal carotid nerve. The postganglionic fibres innervating the nasal mucosa had a similar threshold to those of the nictitating membrane, which may indicate that there are small myelinated fibres innervating the mucosa.The preganglionic compound nerve action potential had four major components, S₁–S₄. S₁, S₂ and usually S₃ fibres were associated with membrane contraction; S₂, S₃ and sometimes S₁ fibres were associated with nasal vasoconstriction; and S₃, usually S₂ and occasionally S₁ fibres were associated with vasoconstriction in the tongue. It is concluded that each of these three groups of nerve fibres, but not S₄ fibres, may include fibres associated functionally with the three effectors.There was a considerable difference between the relative amplitude of the responses of the three effectors elicited by stimulation of the cervical sympathetic nerve at frequencies between 0.2 and 2 Hz. Vasoconstrictor responses were relatively larger than membrane contractions suggesting differences in the mechanisms of neurotransmission at the neuroeffector junctions.     

Development of the projection from the nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret

Neurons in the deeper layers of the superior colliculus (SC) have spatially tuned receptive fields that are arranged to form a map of auditory space. The spatial tuning of these neurons emerges gradually in an experience-dependent manner after the onset of hearing, but the relative contributions of peripheral and central factors in this process of maturation are unknown. We have studied the postnatal development of the projection to the ferret SC from the nucleus of the brachium of the inferior colliculus (nBIC), its main source of auditory input, to determine whether the emergence of auditory map topography can be attributed to anatomical rewiring of this projection. The pattern of retrograde labeling produced by injections of fluorescent microspheres in the SC on postnatal day (P) 0 and just after the age of hearing onset (P29), showed that the nBIC-SC projection is topographically organized in the rostrocaudal axis, along which sound azimuth is represented, from birth. Injections of biotinylated dextran amine-fluorescein into the nBIC at different ages (P30, 60, and 90) labeled axons with numerous terminals and en passant boutons throughout the deeper layers of the SC. This labeling covered the entire mediolateral extent of the SC, but, in keeping with the pattern of retrograde labeling following microsphere injections in the SC, was more restricted rostrocaudally. No systematic changes were observed with age. The stability of the nBIC-SC projection over this period suggests that developmental changes in auditory spatial tuning involve other processes, rather than a gross refinement of the projection from the nBIC.     

A contribution to the study of the architecture of the autonomic nervous system of the digestive tract of the rat

Summary The distribution of aminergic and non-aminergic nerve fibres to the different constituents of the wall of the digestive tract in various regions is described. Aminergic fibres synapse with all nervous perikarya. Densely interlacing networks of nerve fibres are found in both layers of the tunica muscularis and in the lamina muscularis mucosae. A finely meshed plexus is observed in relation to the wall of the blood vessels in the wall of the gut. There are many fibres connecting the muscular and the vascular plexus. No nerve fibres have been observed in direct relation to the epithelium.The functional implications of these findings are discussed.