帕金森病伴发抑郁的神经递质改变

目的探讨帕金森病伴发抑郁的神经递质改变.方法用抑郁自评量表(CESD)和汗密尔顿抑郁量表(HAMD)评出帕金森病伴发抑郁患者33例,其中轻度抑郁24例,重度抑郁9例;另取阑尾炎、腹股沟疝、内、外混合痔等25例为对照组.应用日本岛津6A高效液相色谱仪,岛津电化学检测器对两组患者进行了脑脊液(CSF)中单胺类神经递质代谢产物5-羟吲哚已酸(5-HIAA)和3-甲氧-4羟苯乙二醇(MHPG)的含量测定.并进行统计处理.结果两组均数用近似法t检验,(两总体方差不齐)以-x±S表示,结果显示患者组中的5-HIAA和MHPG含量均低于对照组,差异有非常显著性.结论本组通过测定5-HT的代谢产物5-HIAA和NA的代谢产物MHPG,证实了PD伴发患者抑郁的患者其CSF中5-HIAA和MHPG含量显著减少,抑郁症状被认为与5-HT和(或)NA的缺乏有关.本文显示PD伴发抑郁有其生化病理基础.     

盐酸帕罗西汀对脑卒中后束缚应激大鼠行为学和下丘脑内单胺递质的影响

目的:探讨盐酸帕罗西汀对脑卒中后束缚应激大鼠脑内单胺递质的影响.方法:建立脑卒中后束缚应激大鼠模型,观察各组大鼠糖水消耗试验、自发性行为改变和下丘脑单胺类神经递质的变化.结果:模型组大鼠蔗糖水饮用量、旷野实验水平及垂直得分、下丘脑NE、5-HT、DA含量等与正常组相比明显减少;帕罗西汀组大鼠糖水饮用量、旷野实验中的得分和下丘脑神经递质的含量较模型组大鼠明显增加.结论:盐酸帕罗西汀对脑卒中后束缚应激大鼠模型的作用可能与增加下丘脑单胺类神经递质的含量有关.     

慢性应激对大鼠行为学及脑神经颗粒素水平的影响及药物防治

目的探讨慢性应激对大鼠外显行为学变化的影响,检测体内儿茶酚胺类物质及神经颗粒素(Neurogranin,Ng)表达的变化及三七皂苷Rg1的防治效果。方法成年雄性SD大鼠36只,随机分为对照组(CON)、模型组(CUS)、和治疗组(CUS-G),采用慢性不可预见性应激方法建立慢性应激动物模型;采用旷场试验检测行为学变化,运用Morris水迷宫实验进行学习记忆力测试,使用放射免疫法检测血浆、脑组织儿茶酚胺类含量,Western blot法检测皮质、海马、下丘脑Ng含量。结果 6 w慢性应激后,实验组大鼠在水平运动和垂直运动方面得分均明显低于对照组与药物组,均P0.05;水迷宫实验显示慢性应激后动物逃避潜伏期明显延长,而治疗组大鼠逃避潜伏期呈下降趋势(P0.05);血浆、脑组织去甲肾上腺素与多巴胺在对照组、实验组与药物组间无明显变化;慢性应激大鼠皮质、海马、下丘脑Ng含量水平皆与模型大鼠有差异(P0.05、P0.01、P0.05),治疗大鼠皮质、海马、下丘脑Ng含量亦皆与模型大鼠有差异(P0.01、P0.05、P0.05)。结论慢性应激研究领域,神经颗粒素的敏感性优于单胺类神经递质,可作为敏感指标加以观察;100 mg/kg剂量的三七皂苷Rg1能够抑制应激所致学习记忆功能紊乱,对应激所致外显行为有积极的调节作用,对脑内神经颗粒素表达水平降低趋势有较好抑制作用。     

β-淀粉样蛋白致大鼠衰老模型及单胺类递质改变

目的 :建立β-淀粉样蛋白 (β- AP)致大鼠衰老模型 ,并观察大鼠学习、记忆功能及单胺类递质的改变。方法 :2 0只 SD大鼠被随机分为β- AP组 (10只 )和照组 (10只 )。在β- AP组大鼠双侧海马内各注射β- AP10μg,对照组注射等量生理盐水。 1周后用三等分迷宫测大鼠的学习、记忆功能 ;进行旷场实验观察其探究活动能力和紧张度 ;随后处死大鼠 ,检测海马内单胺类神经递质的浓度。结果 :β- AP组的学习、记忆功能和探究活动与对照组相比明显降低 (P<0 .0 5或 P<0 .0 0 1)。海马内 3-甲基 4-羟基苯乙醇 (MHPG)、 5羟吲哚乙酸 (5 - HIAA)水平比照组明显下降 (均 P<0 .0 1) ,但高香草酸 (HVA)水平无明显下降。结论 :β- AP致大鼠衰老模型是一种较成功的 Alzheimer病 (AD)动物模型     

帕金森病患者立体定向手术前后脑脊液单胺类递质含量的改变

目的　研究帕金森病 (PD)患者脑立体定向手术前后脑脊液 (CSF)中单胺类递质含量的变化。方法测定 2 6例原发性PD患者 (PD组 )脑立体定向术前、后CSF中多巴胺 (DA)、5 羟色胺 (5 HT)、去甲肾上腺素 (NE)及其代谢产物高香草酸 (HVA)、5 羟吲哚乙酸 (5 HIAA)、3 甲氧基 4羟基苯乙二醇 (MHPG)的含量 ,另外测定 2 5例外科疾病腰麻手术患者 (对照组 )CSF中HVA、5 HIAA、MHPG含量。结果　PD组CSF中HVA、5 HIAA、MHPG含量明显低于对照组 (P <0 0 0 1、P <0 0 5、P <0 0 0 1) ;手术后组的CSF中DA、HVA ,、5 HT、5 HIAA、NE、MHPG含量明显高于手术前组 (其中DA、HVA、5 HT、5 HIAA和NE均P <0 0 0 1;MHPGP <0 0 5 )。结论　PD患者CSF单胺类神经递质代谢产物含量明显降低 ,脑立体定向术可提高PD患者脑部单胺类神经递质及其代谢产物的含量 ,其发生机制可能与DA能神经元的保护作用有关     

不同程度颈动脉狭窄大鼠模型建立及脑内单胺类递质变化的研究

周振华,陈康宁,黄河清,周宇,范文辉,李露斯摘要:目的制作一种新的不同狭窄程度的大鼠颈动脉狭窄模型,观察重度颈动脉狭窄大鼠学习能力及脑内单胺类神经递质含量的变化。方法采用“针控线拴法”,通过调整针的型号来制作不同狭窄程度的大鼠颈动脉狭窄模型,观察重度颈动脉狭窄大鼠水迷宫定位航行试验并用高效液相色谱法测定大鼠脑内单胺类神经递质含量的变化。结果成功制作了轻、中、重不同狭窄的颈动脉狭窄模型;各时相点水迷宫定位航行试验中重度颈动脉狭窄大鼠较假手术对照组逃避潜伏期明显延长(P<0.01);除1月、2月重度颈动脉狭窄组DA与假手术对照组相比无显著性差异外(P>0.05),其余时相点重度颈动脉狭窄组NE、5-HT、DA含量与假手术对照组相比均显著降低(P<0.01)。结论针控线拴法能成功建立不同狭窄程度的大鼠颈动脉狭窄模型,重度颈动脉狭窄大鼠学习能力受损且脑内单胺类神经递质含量降低。     

病毒性脑炎患者脑脊液5-羟色胺、多巴胺改变及其与精神异常的关系

目的探讨病毒性脑炎患者脑脊液5-羟色胺(5-HT)、多巴胺(DA)等的改变及其与精神异常的关系。方法采用高效液相色谱法(HPLC)检测69例病毒性脑炎患者和21例其他疾病患者对照脑脊液的5-HT、DA及其代谢产物5-羟吲哚乙酸(5-HIAA)和高香草酸(HVA)的水平。结果①患者组脑脊液的5-HT、5-HIAA和5-HIAA/HVA比值明显低于对照组(P<0.01),5-HT/DA比值低于对照组(P<0.05),而HVA明显高于对照组(P<0.01)。②患者组划分亚组后进一步比较的结果显示,除无精神异常组的5-HT和对照组的差异无统计学意义外(P>0.05),其余上述指标有或无精神异常组与对照组的差异均有统计学意义(P<0.05);有精神异常组脑脊液中的5-HIAA低于无精神异常组(P<0.05);阳性症状为主组脑脊液中的5-HT、5-HIAA、5-HT/DA和5-HIAA/HVA比值低于阴性症状为主组(P<0.05),5-HT、5-HIAA和5-HIAA/HVA比值低于无精神异常组(P<0.05),而阴性症状为主组与无精神异常组各指标差异无统计学意义。结论病毒性脑炎患者脑脊液中可能存在5-HT和DA功能失衡,且这种失衡可能与患者出现的精神症状有关。     

抑郁症患者自杀与脑脊液单胺代谢产物的关系

目的：探讨抑郁症患者自杀与脑脊液单胺代谢产物之间的关系。方法：应用高效液相色谱法，测定24例抑郁症患者(自杀组10例，无自杀组14例)及25例对照组5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)，去甲肾上腺素(NE)代谢产物3-甲基-4-羟苯乙二醇(MHPG)及多巴胺(DA)代谢产物高香草酸(HVA)的浓度。结果：抑郁症自杀组5-HIAA浓度显著低于对照组，男性自杀组5-HIAA浓度、HVA浓度和HVA／MHPG比值均显著低于男性对照组，女性则无显著差异：结论：抑郁症患者自杀可能与5-HT和DA功能低下以及DA和NE之间的关系改变有关。     

全脑缺血后海马区单胺类神经递质的变化

目的观察全脑缺血后大鼠海马区单胺类神经递质的变化规律,探讨其在缺血后迟发性神经元死亡中的作用。方法建立大鼠全脑缺血再灌注模型,观察全脑缺血再灌注后酪氨酸羟化酶(TH)、多巴胺-β-羟化酶(DβH)的表达并对海马区去甲肾上腺素(NE)、肾上腺素、多巴胺、5-羟色胺(5-HT)和单胺类神经递质代谢产物高香草酸(HVA)、5-羟吲哚乙酸(5-H IAA)的含量进行测定。结果对照组TH及DβH呈阴性表达。全脑缺血再灌注后1 d,3 d缺血组海马CA1区神经元TH及DβH表达阴性。5 d后神经元TH及DβH呈阳性表达;全脑缺血再灌注后6 h,缺血组海马区单胺类神经递质含量显著上升,NE、肾上腺素、多巴胺及5-HT分别为对照组的232.5%、347.3%、336.1%和210.1%,1 d后开始回落,3 d已明显低于对照组,5 d后又有回升并接近对照组;缺血组,海马区单胺类神经递质的代谢产物HVA、5-H IAA含量于全脑缺血再灌注后6 h开始上升,1 d依然保持较高的水平,至3 d回落,5 d接近对照组。结论全脑缺血再灌注后早期海马区单胺类神经递质含量显著上升;单胺类神经递质含量显著上升可能是导致迟发性神经元死亡的主要因素之一。     

慢性束缚应激对大鼠体质量、血清皮质酮和前额叶皮质cAMP-PKA-CREB-BDNF通路的影响

目的探讨慢性束缚应激对大鼠体质量、血清皮质酮水平和前额叶皮质cAMP-PKA-CREB-BDNF通路的影响。方法将30只雄性SD大鼠随机分为对照组、慢性束缚应激1周组和慢性束缚应激2周组,每组各10只。比较应激前后大鼠体质量和血清皮质酮水平的变化,放免法观察应激前后大鼠前额叶皮质环磷腺苷(cAMP)含量,试剂盒测定cAMP依赖蛋白激酶(protein kinase,PKA)活性和脑源性神经营养因子(brain derived neurophic factor,BDNF)表达水平,用蛋白免疫印迹技术观察cAMP反应元件结合蛋白质(p-CREB)水平变化。结果慢性束缚应激组大鼠在应激1周和应激2周的体质量增长[分别为(35±11)g和(23±8)g]均低于对照组[分别为(59±16)g和(68±14)g](P<0.05)。束缚应激1周组和束缚应激2周组大鼠血清皮质醇浓度分别为(356.78±112.21)ng/ml、(558.49±98.32)ng/ml,均高于对照组(198.21±101.35)ng/ml(P<0.05,P<0.01)。束缚应激1周组和束缚应激2周组大鼠前额叶皮质的cAMP含量、PKA活性、p-CREB和BDNF表达水平低于对照组(P<0.01)。结论慢性束缚应激抑制大鼠体质量的增长,引起血清皮质酮水平增高和前额叶皮质cAMP-PKA-CREB-BDNF信号通路被抑制。     

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.     

Summary of legislation of 1935 of interest to the department of Mental Hygiene

Psychiatric Quarterly -     

Summary of legislation of 1941 of interest to the Department of Mental Hygiene

Psychiatric Quarterly -     

Asymmetry of on- and off-pathways of blue-sensitive cones of the retina of macaques

Macaque retinal ganglion cells whose receptive-field center recieves input from blue-sensitive cones show an overt asymmetry of the frequency of ON-center and OFF-center varieties, an asymmetry not present in ganglion cells whose center receives input from the other two cone types. A similar asymmetry of ON/OFF responses is found in the local electrotetinogram (d-wave) mediated by signals from blue-sensitive cones. ‘Blue-ON-center’ ganglion cells have larger receptive-field centers and shorter conduction latencies than other opponent-color varieties, suggesting an appreciable degree of receptor convergence and presumably large cell bodies. Intracellular stainings of these neurons with Procion Yellow show that they correspond to diffuse stratified (Parasol) ganglion cells whose flat-topped dendritic arborization stratifies in the sclerad half of the inner plexiform layer. In view of the known characteristics of macaque bipolar cells and of the ON/OFF asymmetry, it is proposed that these ganglion cells are postsynaptic to cone-specific flat bipolars possibly mediating sign-inverting synaptic contacts. The results also indicate a reversal, for the blue-cone pathway, of the ON/OFF lamination of the inner plexiform layer that has recently been described in other species.     

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.