法舒地尔对戊四氮点燃大鼠海马丝切蛋白及苔藓纤维出芽的影响

目的 探讨法舒地尔对戊四氮(PTZ)点燃大鼠海马组织中丝切蛋白(cofilin,非磷酸化形式)表达与苔藓纤维出芽程度关系的影响.方法 210只SD雄性大鼠分成戊四氮组、法舒地尔干预组和生理盐水对照组,采用PTZ慢性点燃癫癎模型,应用SABC法检测cofilin表达,用Timm染色检测苔鲜纤维出芽情况.结果 PTZ组大鼠点燃率、病死率与法舒地尔组比较差异无统计学意义.PTZ组和法舒地尔组CA3区苔藓纤维出芽评分差异无统计学意义,与对照组相比差异均有统计学意义(P＜0.05).PTZ组和法舒地尔组海马非磷酸化cofilin表达差异无统计学意义.结论 丝切蛋白可能通过苔藓纤维出芽与癫癎的发生相关.     

戊四氮点燃模型大鼠GSK-3β活性的动态变化及其与苔藓纤维出芽的关系

目的 探讨戊四氮点燃模型大鼠GSK-3β活性变化与苔藓纤维出芽的关系.方法 取戊四氮点燃模型大鼠给药后3 d、1、2、4和6周的脑片,通过Timm染色观察苔藓纤维出芽的动态变化;取各时间点的大鼠海马组织,通过酶活性测定方法 检测GSK-3β活性变化.结果 戊四氮组各时间点GA3区苔藓纤维出芽评分均有显著性差异(P＜0.05);从3 d起评分逐渐增加,2周时达高峰并维持至6周.在点燃过程中海马GSK-3β蛋白活性逐渐增高,2周达高峰,4、6周表达逐渐下调到生理盐水对照组水平,除6周组外各时间点与相应时间点生理盐水对照组比较差异均有统计学意义.结论 GSK-3β通过活性上调参与了苔藓纤维出芽过程,促进了癫(癎)的发生.     

颞叶癫(癎)大鼠海马轴突导向分子Sema3F及其受体Np2表达的变化

目的研究颞叶癫大鼠海马轴突导向分子Sema3F及其受体Np2表达的变化。方法给SD大鼠腹腔注射匹罗卡品、氯化锂制作颞叶癫模型。用免疫组化法和原位杂交技术对致后不同时间点大鼠海马CA1区、CA3区、齿状回的Sema3F mRNA、Np2 mRNA和蛋白表达进行检测,并与正常对照组比较。结果颞叶癫大鼠致后7d、15d,海马CA1区、CA3区Sema3F mRNA、Np2 mRNA和蛋白的表达明显低于正常对照组(P<0.05~0.01),致后30d、60d表达与正常对照组差异无统计学意义;而齿状回Sema3F mRNA、Np2 mRNA和蛋白的表达与正常对照组的差异无统计学意义。结论颞叶癫大鼠海马CA1区、CA3区Se-ma3F、Np2表达在致后早期明显下调,而在慢性期恢复正常。     

戊四氮点燃癫(癎)大鼠海马巢蛋白和骨形成蛋白-4的表达研究

目的观察巢蛋白(nestin)和骨形成蛋白4(BMP4)基因在戊四氮(PTZ)点燃癫大鼠海马中的表达,并探讨两者与癫发病机制的关系。方法将81只成年雄性SD大鼠随机分为实验组(n=54)和对照组(n=27)。实验组采用PTZ点燃癫大鼠,按点燃中的不同时相点,又随机分为9组。用免疫组化技术、地高辛标记特异性寡核苷酸探针原位杂交组织化学技术,观察海马nestin和BMP4表达的变化。结果nestin阳性细胞在PTZ注射后3d开始出现在齿状回、CA3区和CA1区,到7d达到高峰,以后逐渐减少。BMP4在PTZ注射后7d开始增多,在点燃后1d达到高峰,以后逐渐减少,主要分布在齿状回、CA3区和CA1区。结论PTZ点燃可引起海马内星形胶质细胞增生、活化和神经发生,这可能是癫海马组织胶质化、神经元可塑性的病理基础;BMP4可能在PTZ癫形成过程中起重要作用。     

戊四氮致痫大鼠海马GSK-3β表达与苔藓纤维出芽关系研究

目的观察戊四氮(PTZ)致痫大鼠海马各区糖原合成酶激酶-3β(GSK-3β)蛋白及其mRNA表达和苔藓纤维出芽(MFS)情况,探讨GSK-3β在癫痫发病机制中的作用。方法SD雄性成年大鼠120只,随机分为实验组和对照组;实验组分为PTZ第1次注射后3d、1w、2w、4w、6w共5个亚组,每亚组12只。对照组同样随机分为5个亚组,每亚组12只,与实验组各时间点对应。以上各亚组再分2个小组,每小组6只大鼠,分别进行(1)GSK-3β的免疫组化和原位杂交染色并测定其相应的光密度值;(2)Timm染色并评分。结果实验组大鼠海马各区GSK-3β蛋白及其mRNA表达在点燃过程中逐渐增多,点燃后表达逐渐下调到正常对照组水平,在点燃前后除6w组外GSK-3β表达与对照组相应时间点比较差异有统计学意义(P<0.05);实验组CA3区在点燃前可见1~4级MFS,点燃后可见4~5级MFS;癫痫点燃过程中CA3区GSK-3β表达与MFS评分有线性正相关关系。结论GSK-3β在海马表达变化可能在苔藓纤维出芽的过程中起促进作用,从而促进癫痫的发生。     

发育期癫大鼠移植骨髓源性神经干细胞对海马BDNF和bFGF表达的影响

目的将骨髓源性神经干细胞(BMSCs)移植到发育期癫大鼠海马区,观察大鼠海马脑源性神经营养因子(BDNF)和碱性成纤维生长因子(bFGF)表达的变化。方法选择21日龄发育期大鼠,分离大鼠骨髓基质细胞,在特定条件下培养使其诱导分化为神经干细胞(NSC)。建立戊四氮(PTZ)点燃癫大鼠模型,将BMSCs经侧脑室注射移植至癫大鼠海马区;侧脑室注射磷酸缓冲液(PBS)作为对照。分为4组(均n=8):对照组(无癫发作),PTZ致组(癫造模,无治疗),假手术组(癫+PBS侧脑室注射),治疗组(癫+NSC侧脑室注射)。于3、7和14 d处理后用免疫组化法检测大鼠海马区BDNF和bFGF表达。结果致组大鼠海马区(齿状回、CA1区)BDNF和bFGF表达较对照组增加(P0.05),治疗组海马区(齿状回、CA1区)BDNF和bFGF表达较假手术组也有所增加(P0.05)。结论 BMSCs移植可以增加PTZ致大鼠海马BDNF和bFGF表达,从而发挥对癫后脑损伤的保护作用。     

银杏叶提取物对戊四氮致大鼠海马内NMDA受体和HSP70表达的影响

目的探讨银杏叶提取物抗癫的分子生物学机制。方法在SD大鼠腹腔内注射戊四氮(PTZ)诱发大鼠惊厥急性发作,制作癫模型。应用免疫组化技术观察银杏叶提取物(GBE)对点燃癫大鼠海马内NMDA受体和HSP70表达的影响。结果戊四氮致组大鼠海马内NMDA受体表达明显高于正常对照组,银杏叶提取物干预组明显低于戊四氮致组,银杏叶提取物干预组与正常对照组之间差异无显著性意义。戊四氮致组大鼠海马内HSP70表达明显高于正常对照组,银杏叶提取物干预组明显高于戊四氮致组。结论银杏叶提取物可降低癫大鼠海马内NMDA受体的表达,其可能通过此种机制来抑制癫的发生和发展。银杏叶提取物可增加癫大鼠海马内HSP70的表达,以此来减轻癫发作后所致的神经元损伤。     

红藻氨酸致颞叶癫(癎)大鼠脑内Semaphorin3A、Semaphorin4C基因表达的研究

目的研究轴索导向分子Semaphorin3A(Sema3A)、4C(Sema4C)对癫大鼠海马苔藓纤维重建的调控作用及对皮层神经元的保护作用。方法大鼠侧脑室内注射红藻氨酸制备颞叶癫模型,原位杂交法检测致痫间后1d,1、2、3、4周大鼠脑内Sema3A/Sema4C mRNA表达。结果致痫间后1周Sema3A、Sema4CmRNA分别在齿状回(DG),CA3区表达明显下降(P<0.01),持续至3、4周时恢复至正常(P>0.05);致痫间后1d Sema3A mRNA在皮层表达明显下降(P<0.01),持续至1、2周后恢复至正常(P>0.05)。结论红藻氨酸致痫间后DG及CA3区神经元分别下调Sema3A/Sema4C mRNA的表达,促进癫大鼠苔藓纤维重建;皮层神经元通过下调Sema3A mRNA的表达来维持自身存活。     

戊四氮点燃癫癎大鼠空间学习记忆改变及海马NR2B表达

目的观察戊四氮点燃癫癎大鼠空间学习记忆功能变化及海马NMDA2型受体(NR2)B亚单位(NR2B)表达,探讨二者的关系及PTZ致癎大鼠认知障碍发生的分子机制。方法采用戊四氮(PTZ)慢性癫癎(CE)模型,Y-迷宫对两组大鼠进行行为学检测,免疫组织化学方法观察两组大鼠海马CA3区NR2B表达的变化,反转录多聚酶链反应(RT-PCR)方法检测大鼠海马NR2B mRNA的表达。结果癫癎组大鼠空间学习记忆能力受损;其海马CA3区NR2B阳性细胞较对照组明显减少(P<0.01),同时伴有海马NR2B mRNA表达下降(P<0.01)。结论戊四氮点燃癫癎大鼠空间学习记忆受损可能与海马神经元NR2B的表达减少有关。     

戊四氮点燃模型大鼠Cdk5活性与苔藓纤维出芽相关性

目的研究戊四氮(PTZ)点燃模型大鼠细胞周期素依赖性激酶5(Cdk5)活性改变与苔藓纤维出芽(MFS)动态变化的相关性。方法将120只雄性成年大鼠随机分为PTZ组和对照组,PTZ组连续每天腹腔注射PTZ30mg/kg,对照组同时注射等体积生理盐水。按戊四氮第1次给药后3d、1、2、4和6周各随机分为5个亚组。每个亚组再随机分为2个小组:一组用于液体闪烁计数仪测定各时间点大鼠海马的Cdk5活性;另一组用于Timm染色检测苔藓纤维出芽情况。结果 PTZ组MFS评分3d时增加,2周达高峰并维持至6周;海马Cdk5活性3d时增加,2周达高峰,4周下降,6周恢复对照组水平;较对照组有显著差异。额区Cdk5活性各时间点之间及与对照组之间均无显著性差异。结论 Cdk5可能通过活性增高参与苔藓纤维出芽,从而促使癫发生。     

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 -