Membrane Localization of Endopeptidase-24.11 and Peptidyl Dipeptidase A (Angiotensin Converting Enzyme) in the Pig Brain: A Study Using Subcellular Fractionation and Electron Microscopic Immunocytochemistry

Brains from piglets were dissected and a block of tissue including the substantia nigra, globus pallidus, and entopeduncular nucleus was homogenized and then fractionated on discontinuous Percoll gradients. Ligand-binding assays using (-)-[3H]nicotine and [3H]quinuclidinyl benzilate served to delineate fractions containing nicotinic and muscarinic acetylcholine receptors. In this system endopeptidase-24.11 exhibited a biphasic distribution, consistent with its presence on both pre- and postsynaptic membranes. Peptidyl dipeptidase A (angiotensin converting enzyme; ACE) was associated with membrane fractions containing muscarinic receptors. An immunoblot of these fractions with an affinity-purified polyclonal antibody to ACE revealed only the neuronal form of ACE (Mr 170,000), the endothelial form (Mr 180,000) being undetectable. Electron microscopic immunoperoxidase staining of the substantia nigra, with an affinity-purified antibody to endopeptidase-24.11 at the preembedding stage, showed this antigen to be confined to the plasma membranes of boutons, axons, and some dendrites. Both pre- and postsynaptic membranes were stained, and occasionally other regions of the dendritic membrane were positive. No staining of synaptic vesicles within the boutons was observed. Thus, two independent approaches indicate that endopeptidase-24.11 is present on both pre- and postsynaptic membranes in the pig substantia nigra. The subcellular fractionation suggests that neuronal ACE is confined to dendritic membranes.     

Pathological changes in dendrites of substantia nigra neurons in Parkinson's disease: a Golgi study.

Neurons of the substantia nigra show severe morphological changes in Parkinson's disease. Pathological alterations of cell bodies have been described, whereas those of neuronal processes have hardly been investigated. Golgi impregnation has been the chosen method for demonstrating neuronal processes and dendritic and somatic spines. We therefore used the Golgi-Braitenberg method to qualitatively and semi-quantitatively study the substantia nigra of eight patients with Parkinson's disease compared with eight control cases. Golgi impregnation of substantia nigra neurons was good in all control cases. In full agreement with the analysis of Braak and Braak (1986) three neuronal types within the substantia nigra were found. In cases of Parkinson's disease, severe pathological changes such as decrease of dendritic length, loss of dendritic spines and several types of dendritic varicosities were found only in the melanin-containing pars compacta neurons. Pars reticulata nerve cells were intact. These findings support the predominant role played by the dopaminergic efferent pathway in the degenerative process. The afferent pathway was not affected. This suggests that the substantia nigra lesion is primary in Parkinson's disease. Loss of neurons found in H & E sections corresponded to a lesser amount of impregnated pars compacta neurons in cases with Parkinson's disease when compared to controls. Evidences exist that the duration of the disease may be related to the extent of pathologically altered Golgi-impregnated pars compacta cells. The amount of Lewy bodies in H & E sections corresponded to the quantity of round varicosities in impregnated pars compacta neurons. These round dendritic varicosities were considered to be Lewy body inclusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for a nigro-pulvinar-lateralis posterior complex projection in the cat using horseradish peroxidase neuronal retrograde technique

The possible existence of a direct projection from the substantia nigra to the pulvinar-lateral posterior complex (Pul-LP) was investigated in the cat by using the horseradish peroxidase technique. In particular horseradish peroxidase was injected in the Pul-LP of 8 animals, either unilaterally or bilaterally. Tissue sections obtained from the cat's brain 24-48 hrs. after injection were prepared according to Mesulam's method as slightly modified by the authors. Retrogradelly labelled neurons were observed in substantia nigra pars lateralis and reliculata ipsilaterally to the injected pulvinar-lateral posterior complex. A small number of labelled cells were also found in the contralateral substantia nigra. These findings demonstrate the existence of a close connection between two system which are involved in turning behavior: the nigrostriatal and the pulvinar-lateral posterior complex-superior colliculus.     

GABAA Receptors in the Pars Compacta and GABAB Receptors in the Pars Reticulata of Rat Substantia Nigra Modulate the Striatal Dopamine Release

The nigral GABAergic regulation of striatal dopamine release was investigated using voltammetry in freely moving rats. The local administration of muscimol (1 nM) in the substantia nigra pars compacta, but not in the substantia nigra pars reticulata, increased the striatal dopamine release. In contrast, the administration of baclofen (10 nM) in the substantia nigra pars reticulata, but not in the substantia nigra pars compacta, produced a decrease of the striatal dopamine release. Opposite effects were respectively observed after administration of GABA_A and GABA_B antagonists. These data lead us to suggest a differential presynaptic GABAergic control of the dopaminergic neurotransmission through GABA_A receptors in the substantia nigra pars compacta, and GABA_B receptors in the substantia nigra pars reticulata.     

Electron microscopic study of the substantia nigra and the strio-nigral projection in the rat

Summary The normal ultrastructure of rat substantia nigra was investigated. Special attention was paid to the different types of boutons, and the mode of termination of the striatonigral connection was examined. Two different types of nigra neurons with deep nuclear membrane indentations were observed. The synaptic organization of rat substantia nigra is very complex. Six types of boutons, with many characteristics, could be differentiated: pleomorphicvesicle boutons (40%), elongated-vesicle boutons (10%), small-round-vesicle boutons (10%), large-round-vesicle boutons (20%), clear-terminal (15%) and dense-core-vesicle boutons (about 5%). Vesicle-containing dendrites were observed entering dendro-dendritic synapses. One to four days after large unilateral striatal lesions were made, a great number of degenerating boutons were seen in the ipsilateral substantia nigra, while the contra-lateral substantia nigra was entirely free of degeneration. The newly defined pleomorphic-vesicle boutons were found almost exclusively in the process of degeneration. The neuronal origin of the other bouton types is discussed.On leave of absence from Anatomical Institut, Semmelweis University, Budapest.     

Characterization and visualization of neurotensin binding to receptor sites in human brain

The binding of monoiodo [125I-Tyr3]-neurotensin to human brain was characterized and visualized using radioreceptorassay and autoradiographic techniques. Specific binding to homogenates of human substantia nigra at 25 degrees C was maximal at 20 min, reversible and saturable. Scatchard analysis of equilibrium data indicated the existence of two populations of binding sites with Kd values of 0.26 nM and 4.3 nM. Corresponding binding capacities were 26 and 89 fmol/mg of protein. Neurotensin analogs inhibited the binding of iodinated neurotensin with relative potencies that demonstrated the crucial role of the C-terminal hexapeptide portion of neurotensin for binding to its receptors. Autoradiography of human substantia nigra sections incubated with iodinated neurotensin revealed high levels of specific binding in the nucleus paranigralis and substantia nigra, pars compacta, and low levels in the substantia nigra, pars reticulata.     

The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice

Tyrosine kinase receptors TrkB and TrkC mediate neuroprotective effects of the brain-derived neurotrophic factor (BDNF) and neurotrophins in the dopaminergic nigro-striatal system, but it is obscure about their responses or expression changes in the injured substantia nigra under Parkinson’s disease. In present study, immunofluorescence, Fluoro-Jade staining and laser scanning confocal microscopy were applied to investigate distribution and changes of TrkB and TrkC in the dopamine neurons of the substantia nigra by comparison of control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. It revealed that TrkB and TrkC-immunoreactivities were substantially localized in cytoplasm and cell membrane of the substantia nigra neurons of control adults. While neurons double-labeled with tyrosine hydroxylase (TH)/TrkB, or TH/TrkC were distributed in a large numbers in the substantia nigra of controls, they apparently went down at 36.2–65.7% of normal level, respectively following MPTP insult. In MPTP model, cell apoptosis or degeneration of nigral neurons were confirmed by caspase-3 and Fluoro-Jade staining. More interestingly, TH/TrkB-positive neurons survived more in cell numbers in comparison with that of TH/TrkC-positive ones in the MPTP model. This study has indicated that TrkB-containing dopamine neurons are less sensitive in the substantia nigra of MPTP mouse model, suggesting that specific organization of Trks may be involved in neuronal vulnerability to MPTP insult, and BDNF-TrkB signaling may play more important role in protecting dopamine neurons and exhibit therapeutic potential for Parkinson’s disease.     

Time Course Changes in the Dopaminergic Nigrostriatal System Following Transection of the Medial Forebrain Bundle: Detection of Oxidatively Modified Proteins in Substantia Nigra

Abstract: We studied the time course of oxidatively modified proteins in the nigrostriatal dopaminergic system following transection of the medial forebrain bundle by quantifying the number of carbonyl groups coupled to striatal and nigral protein homogenates, an index of metal-catalyzed oxidations. We found a striking effect of axotomy on the number of oxidatively modified proteins in the substantia nigra but not in the striatum within the first 5 days postlesion. This effect was correlated with the neurochemical activity of the dopaminergic and serotoninergic systems in the substantia nigra, which suggests a role of dopamine- and serotonin-derived radical oxygen species in the oxidative stress detected in this brain area. We then searched for the type of cell death in the substantia nigra following axotomy. The fragmentation pattern obtained by agarose gel electrophoresis of DNA isolated from nigral tissue was indicative of cell death being entirely necrotic. In fact, no evidence of apoptosis was detected at any postlesion time as revealed by TdT-mediated dUTP-biotin nick end-labeling (TUNEL) staining. The course of necrotic cell death in the substantia nigra coincided with the maximal levels of oxidatively modified proteins in the substantia nigra, suggesting a link between oxidative stress and nerve cell death and also coinciding with the neurochemical activity of both dopaminergic and serotoninergic systems.     

Histochemical distribution of non-haem iron in the human brain.

The detailed anatomical distribution of iron in the post-mortem human brain has been studied using Perl's and Turnbull's methods with the diaminobenzidine intensification procedure for the demonstration of non-haem Fe3+ and Fe2+, respectively. Attention to methodological procedures has revealed that even brief immersion of tissue in routinely used fixatives causes a reduction of staining intensity in areas of high iron content and, often, loss of staining in areas of low iron content. Optimal staining is obtained using frozen section briefly fixed for 5 min in 4% formalin and Perl's stain (Fe3+) with diaminobenzidine intensification. Highest levels of stainable iron were found in the extrapyramidal system with the globus pallidus, substantia nigra zona reticulata, red nucleus and myelinated fibres of the putamen showing highest staining reactivity. Moderate staining intensity with Perl's technique was found in the majority of forebrain, midbrain and cerebellar structures with the striatum, thalamus, cortex and deep white matter, substantia nigra zona compacta, and cerebellar cortex showing consistent staining patterns with intensification of Perl's stain. The brain-stem and spinal cord generally only showed staining with the intensification procedure and even this was of low intensity. Microscopically the non-heam iron appears to be found predominantly in glial cells as fine cytoplasmic granules which in heavily stained areas coalesce to fill the entire cell. Iron-positive granules appear to be free in the neuropil and also around blood vessels in the globus pallidus, striatum and substantia nigra. The neuropil shows a fibrous impregnation when stained for iron which is, in part, derived from glial processes, myelinated fibres and fibre bundles. Neurones, in general, show only very low reactivity for iron, and this is difficult to discern due, often, to the higher reactivity of the surrounding neuropil. In the globus pallidus and substantia nigra zona reticulata, neurones with highly stainable iron content are found with granular cytoplasmic iron reactivity similar to that seen in the local glial cells. Our results are comparable with those of early workers, but with the use of intensification extend the distribution of non-haem iron to areas previously reported as negative. No apparent correlation of iron staining with known neurotransmitter systems is seen and the predilection for the extrapyramidal system is not easily explained, though the non-haem iron in the brain appears to be as a storage form in the iron storage protein ferritin. The localization of iron in the brain provides a foundation for the study of iron in certain neurodegenerative diseases such as Parkinson's disease, where iron has been implicated in the pathogenesis.     

Lactacystin诱导帕金森病大鼠黑质胶质细胞的变化

目的观察蛋白酶体抑制剂Lactacystin诱导大鼠黑质胶质细胞的变化、炎性介质NF-κB的表达。方法采用立体定向术将蛋白酶体抑制剂Lactacystin 10μg注射至大鼠黑质部位,免疫组织化学法观察黑质区多巴胺(DA)能神经元、小胶质细胞、星形胶质细胞的变化,炎性介质核转录因子κB(NF-κB)的表达。结果注射Lactacystin 3周,阿朴吗啡腹腔注射后出现典型旋转行为;8周后实验组大鼠损毁侧黑质酪氨酸羟化酶(TH)阳性细胞数明显减少,黑质小胶质细胞及星形胶质细胞的数量均增加,NF-κB表达增强。结论蛋白酶体抑制剂Lactacystin能激活大鼠黑质小胶质细胞及星形胶质细胞,诱导炎性介质表达。     

Combined immuno- and non-radioactive hybridocytochemistry on cells and tissue sections: influence of fixation, enzyme pre-treatment, and choice of chromogen on detection of antigen and DNA sequences

Conditions for combination of DNA in situ hybridization, using biotinylated DNA probes, with immunohistochemistry were investigated on cryostat sections, cytological preparations, and paraffin sections. We found that cryostat sections and cytological preparations are suitable for in situ hybridization of target DNA after fixation in acetone, methanol, ethanol, or Carnoy without further proteinase pretreatment. Acetone is also very suitable for immunostaining of cell surface or cytoskeleton antigens. We therefore performed combined immunoenzyme and in situ hybridization staining using this fixative. The best results were obtained when immunoperoxidase staining with diaminobenzidine/H2O2 was followed directly by in situ hybridization. In addition to immunoperoxidase, alkaline phosphatase-antialkaline phosphatase (APAAP) staining with naphthol ASBI phosphate and New Fuchsin as a substrate could be used. In most instances, detection of the biotinylated hybrid with a streptavidin-biotinylated polyalkaline phosphatase method using nitroblue tetrazolium and 5-bromo-4-chloro-3-indolylphosphate as the substrate was preferable. The double stainings were studied on the following test models: (a) frozen tonsil sections: cell surface antigens (pan T) and ribosomal DNA; (b) frozen genital condyloma sections; cytokeratins and human papillomavirus type 6 + 11 (HPV-6/11) DNA; (c) CaSKi cells: cytokeratins and HPV-16 DNA; (d) infected fetal lung fibroblasts: vimentin and cytomegalovirus (CMV) DNA. An adapted procedure was followed on routinely formaldehye-fixed and paraffin-embedded condyloma tissue. Immunoperoxidase staining for papilloma virus capsid antigen could be combined with DNA in situ hybridization with HPV-6/11 DNA. In this model, however, the accessibility of the target DNA had to be improved by enzyme treatment after the immunostaining and before starting the in situ hybridization.     

Enriched environment protects the nigrostriatal dopaminergic system and induces astroglial reaction in the 6-OHDA rat model of Parkinson's disease

Enriched environment (EE) is neuroprotective in several animal models of neurodegeneration. It stimulates the expression of trophic factors and modifies the astrocyte cell population which has been said to exert neuroprotective effects. We have investigated the effects of EE on 6-hydroxydopamine (6-OHDA)-induced neuronal death after unilateral administration to the medial forebrain bundle, which reaches 85–95% of dopaminergic neurons in the substantia nigra after 3 weeks. Continuous exposure to EE 3 weeks before and after 6-OHDA injection prevents neuronal death (assessed by tyrosine hydroxylase staining), protects the nigrostriatal pathway (assessed by Fluorogold retrograde labeling) and reduces motor impairment. Four days after 6-OHDA injection, EE was associated with a marked increase in glial fibrillary acidic protein staining and prevented neuronal death (assessed by Fluoro Jade-B) but not partial loss of tyrosine hydroxylase staining in the anterior substantia nigra. These results robustly demonstrate that EE preserves the entire nigrostriatal system against 6-OHDA-induced toxicity, and suggests that an early post-lesion astrocytic reaction may participate in the neuroprotective mechanism.     

Synaptic connections of substance P-immunoreactive nerve terminals in the substantia nigra of the rat

Summary A monoclonal antibody that recognises the C-terminal part of substance P was used to study immunoreactive structures in the substantia nigra by the unlabeled antibody, peroxidase-antiperoxidase procedure. Immunoreactivity was present in nerve fibres in all parts of the substantia nigra, particularly in the pars reticulata and pars lateralis. Electron microscopically two types of bouton immunoreactive for substance P were found: Type 1 contained large electron-lucent vesicles, occasional large granulated vesicles and formed symmetrical synapses with dendrites. Type 2 boutons contained smaller, round electron-lucent vesicles, many large granular vesicles and formed asymmetrical synapses (having prominent postjunctional dense bodies) with dendrites and perikarya.Immunoreactive fibres with varicosities that had been identified light microscopically were studied in serial sections in the electron microscope. Each identified varicosity contained synaptic vesicles and formed a single synapse. An individual fibre formed boutons of only one kind (type 1 or type 2) and could form multiple synapses with the same neuron. Thus, an identified fibre in the pars compacta had eight varicosities, each of which was in synaptic contacts (type 2) with the dendrites or soma of the same neuron.The results are consistent with the concept that substance P is a synaptic transmitter in the substantia nigra and indicate that neurons in this region may receive a significant input from substance P-containing afferents, and that there are at least two types of such afferent fibres.     

Biotransformation of l-DOPA to Dopamine in the Substantia Nigra of Freely Moving Rats: Effect of Dopamine Receptor Agonists and Antagonists

Abstract: We investigated the effects of continuous intranigral perfusion of dopamine D1 and D2 receptor agonists and antagonists on the biotransformation of locally applied l -DOPA to dopamine in the substantia nigra of freely moving rats by means of in vivo microdialysis. The "dual-probe" mode was used to monitor simultaneously changes in extracellular dopamine levels in the substantia nigra and the ipsilateral striatum. Intranigral perfusion of 10 µ M l -DOPA for 20 min induced a significant 180-fold increase in extracellular nigral dopamine level. No effect of the intranigral l -DOPA administration was observed on dopamine levels in the ipsilateral striatum, suggesting a tight control of extracellular dopamine in the striatum after enhanced nigral dopamine levels. Continuous nigral infusion with the D1 receptor agonist CY 208243 (10 µ M ) and with the D2 receptor agonist quinpirole at 10 µ M (a nonselective concentration) attenuated the l -DOPA-induced increase in dopamine in the substantia nigra by 85 and 75%, respectively. However, perfusion of the substantia nigra with a lower concentration of quinpirole (1 µ M ) and the D1 antagonist SCH 23390 (10 µ M ) did not affect the nigral l -DOPA biotransformation. The D2 antagonist (−)-sulpiride (10 µ M ) also attenuated the l -DOPA-induced dopamine release in the substantia nigra to ∼10% of that of the control experiments. We confirm that there is an important biotransformation of l -DOPA to dopamine in the substantia nigra. The high concentrations of dopamine formed after l -DOPA administration may be the cause of dyskinesias or further oxidative stress in Parkinson's disease. Simultaneous administration of D1 receptor agonists with l -DOPA attenuates the biotransformation of l -DOPA to dopamine in the substantia nigra. The observed effects could occur via changes in nigral GABA release that in turn influence the firing rate of the nigral dopaminergic neurons.     

Demonstration of laminin, a basement membrane glycoprotein, in routinely processed formalin-fixed human tissues

Laminin was demonstrated by immunoperoxidase and immunofluorescence staining in sections of normal human tissues fixed in formalin and routinely processed in paraffin. Exposure of the sections to a solution of pepsin (Burns et al. (1980) Histochemistry 67:73-78) revealed the antigenicity of this basement membrane glycoprotein. Sections from paraffin blocks stored for years at room temperature could be stained with this procedure. Normal human tissues, developing fetal tissues and tumors could be stained with this method. The staining patterns were similar to those seen in unfixed frozen sections. It thus appears that basement membrane components can be detected by immunohistological means from routinely processed histological samples, once the sections are pretreated with proteases. Staining for laminin could be used in embryonic studies and in histopathology to study the relation of cells to basement membranes and for the visualization of normal and abnormal vascularization.     

Immunocytochemical demonstration of vasopressin binding in rat kidney

We investigated the immunoperoxidase demonstration of vasopressin (VSP) bound to paraffin-embedded sections of rat kidney and the effects of various fixatives. Slices of rat kidney from normal and 4-day water-deprived rats were incubated with 10(-7) M VSP, fixed, and embedded in paraffin. Hydrated sections of these tissues were again incubated with 10(-7) M VSP or 10(-7) M VSP and 10(-5) M oxytocin (OXY). VSP bound to the sections was demonstrated using rabbit anti-Arg8 VSP antiserum and peroxidase-labeled second antibody. In sections of kidney from both normal and water-deprived rats, immunoperoxidase labeling was most intense in the renal papilla and was restricted to the cells of the ducts of Bellini and loops of Henle. In the medulla, the collecting ducts and medullary thick ascending limbs of Henle were moderately stained. In the normal kidney sections there was no staining of the proximal tubules, distal convoluted tubules (DCT), and only slight staining of the cortical collecting ducts (CCD). However, in the water-deprived rats there was a considerable increase in the staining of the DCT and CCD. Simultaneous incubation in OXY and VSP resulted in reduced immunoperoxidase labeling of the tubules. Omission of VSP incubation led to a similar decrease in stain intensity, indicating a specificity for the sites of VSP binding. This technique allows the identification of cells responsible for the binding of VSP in the kidney.     

Botulinum A Like Type B and Tetanus Toxins Fulfils Criteria for Being a Zinc-Dependent Protease

Abstract: Iron is abnormally accumulated in the substantia nigra pars compacta of patients with Parkinson's disease (PD). Because neuronal and glial iron uptake seems to be mediated by the binding of ferrotransferrin to a specific high-affinity receptor on the cell surface, the number of transferrin receptors could be altered in this disease. The regional distribution of specific binding sites for human ¹²⁵I-diferric transferrin has been studied in the mesencephalon, on cryostat-cut sections from autopsy brains of control subjects and parkinsonian patients by in vitro autoradiography. Densities of binding sites were highest in the central gray substance (˜10 fmol/mg of tissue equivalent), intermediate in the catecholaminergic cell group A8, superior colliculus, and ventral tegmental area, and almost nonexistent in the substantia nigra. The density of ¹²⁵I-transferrin binding sites was not significantly different between parkinsonian and control brains in any region analyzed. These results show that in the mesencephalon the regional density of transferrin binding sites is lowest in the dopaminergic cell groups, which are the most vulnerable to PD, and suggest that iron does not accumulate through an increased density of transferrin receptors at the level of the substantia nigra.     

HFE Genotype Restricts the Response to Paraquat in a Mouse Model of Neurotoxicity

Parkinson's disease is marked clinically by motor dysfunction and pathologically by dopaminergic cell loss in the substantia nigra and iron accumulation in the substantia nigra. The driver underlying iron accumulation remains unknown and could be genetic or environmental. The HFE protein is critical for the regulation of cellular iron uptake. Mutations within this protein are associated with increased iron accumulation including in the brain. We have focused on the commonly occurring H63D variant of the HFE gene as a disease modifier in a number of neurodegenerative diseases. To investigate the role of H63D HFE genotype, we generated a mouse model in which the wild‐type (WT ) HFE gene is replaced by the H67D gene variant (mouse homolog of the human H63D gene variant). Using paraquat toxicity as the model for Parkinson's disease, we found that WT mice responded as expected with significantly greater motor function, loss of tyrosine hydroxylase staining and increase microglial staining in the substantia nigra, and an increase in R ₂ relaxation rate within the substantia nigra of the paraquat‐treated mice compared to their saline‐treated counterparts. In contrast, the H67D mice showed a remarkable resistance to paraquat treatment; specifically differing from the WT mice with no changes in motor function or changes in R ₂ relaxation rates following paraquat exposure. At baseline, there were differences between the H67D HFE mice and WT mice in gut microbiome profile and increased L‐ferritin staining in the substantia nigra that could account for the resistance to paraquat. Of particular note, the H67D HFE mice regardless of whether or not they were treated with paraquat had significantly less tyrosine hydroxylase immunostaining than WT . Our results clearly demonstrate that the HFE genotype impacts the expression of tyrosine hydroxylase in the substantia nigra, the gut microbiome and the response to paraquat providing additional support that the HFE genotype is a disease modifier for Parkinson's disease. Moreover, the finding that the HFE mutant mice are resistant to paraquat may provide a model in which to study resistant mechanisms to neurotoxicants.

     

环加氧酶-2对帕金森病小鼠黑质多巴胺能神经元的影响

目的和方法 :选用C5 7BL种系环加氧酶 2 (cyclooxygenase 2 ,COX 2 )缺陷小鼠 ,腹腔注射 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 (MPTP)制备帕金森病小鼠模型 ,用免疫组织化学方法观察COX 2对帕金森病小鼠黑质多巴胺能神经元的影响。结果 :行为学及免疫组织化学观察显示 ,野生型帕金森病小鼠的死亡率明显高于COX 2缺陷杂合子帕金森病小鼠 (P <0 .0 1) ,野生型帕金森病小鼠黑质致密部酪氨酸羟化酶 (tyrosinehydroxylase,TH)免疫反应阳性神经元数目较杂合子帕金森病小鼠明显减少 (P <0 .0 1)。结论 :COX 2可能与帕金森病时黑质多巴胺能神经元的损伤有关     

Role of the substantia nigra in the behavioural-cardiovascular integration in the cat

Electrical stimulation of the substantia nigra elicited complex patterns of response composed of somatomotor and circulatory changes. Increase in blood pressure associated with acceleration in heart rate was consistently produced by substantia nigra stimulation both in conscious and in anaesthetized cats. The respiration was either accelerated or arrested by the stimulation. Also self-stimulation of the substantia nigra elicited pressor responses. Electrical stimulation of the nucleus of the tractus solitarius paired with self-stimulation of the substantia nigra, produced regular changes in the lever-pressing rate for self-stimulation. It is suggested that the substantia nigra is probably involved in the neural mechanisms coupling the circulatory changes with the somatomotor responses.