Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Pathological changes in dendrites of substantia nigra neurons in Parkinson's disease: a Golgi study. 172 60

The central functions of norepinephrine (NE) are a recent discovery: regulation of alertness and of the wakefulness-sleep cycle, maintenance of attention, memory and learning, cerebral plasticity and neuro-protection. The anatomical, histological, biochemical and physiological properties of the central noradrenergic system: extreme capacity for ramification and arborization; slow conduction, non-myelinized axons with extrasynaptic varicosities producing and releasing NE; frequency of co-transmission phenomena, and; neuromodulation with fiber effect responsible for improvement in the signal over background noise ratio and selection of significant stimuli form a true interface between the outside world and the central nervous system, notably for the neocortex in the context of the cognitive treatment of information. This central noradrenergic system is involved in the neurophysiology and the clinical features of cerebral aging (ideation-motor and cognitive function slowing down, loss of behavioral adjustment), neuro-degenerative disorders (SDAT, Parkinson's disease), certain aspects of depression and less obvious conditions (head injuries, sequelae of cerebrovascular accidents, sub-cortical dementia). The recent development of medications improving alertness (adrafinil, modafinil) with a pure central action and specifically noradrenergic, may contribute to an improvement in these multifactorial disorders.
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PMID:[Noradrenaline and cerebral aging]. 186 52

Dopamine projections to the cerebral cortex have been implicated in normal and pathological cognitive processes, notably, Parkinson's disease and schizophrenia. To help elucidate the function of these dopamine axons, they were characterized by serial section electron microscopy in individual layers of monkey prefrontal cortex. Dopamine immunoreactivity was visualized with a silver precipitation technique that allowed clear resolution of the internal structures and cell membranes of labeled axons. Apart from the occasional large microtubule-filled axon, dopamine axons were thin and varicose with many clear synaptic vesicles and fewer dense-core vesicles. With few exceptions, dopamine synapses were symmetric and quite small, seen in only one to three serial sections. A determination of the "synaptic incidence" showed that only 39% of labeled varicosities formed identifiable synapses. However, it is certain that some small synapses could not be visualized even in serial sections, and it is possible that the vast majority if not all varicosities form synapses. Except for one soma, dendritic spines and shafts were the recipients of dopamine synapses. Many postsynaptic shafts were small and spiny, indicating that they were distal pyramidal dendrites. However, some postsynaptic shafts especially in supragranular layers had distinctly nonpyramidal features. These lacked spines, had a high density of synaptic inputs, and often had a strikingly varicose morphology. The data suggest that the majority of dopamine synapses in all layers are on pyramidal cells, but that a significant fraction are on presumed GABAergic nonpyramidal cells.
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PMID:Heterogeneous targets of dopamine synapses in monkey prefrontal cortex demonstrated by serial section electron microscopy: a laminar analysis using the silver-enhanced diaminobenzidine sulfide (SEDS) immunolabeling technique. 768 95

In order to recognize substantia nigra neuronal changes occurring in aging, 20 human control brains from 13 males and 7 females with a mean age of 61 years (range 20 to 93 years) without neurological disease were examined using the Golgi method. A quantitative study of dendrites and dendritic spines was performed as well as a statistical analysis of obtained data. Parallel sections to the impregnated material were histologically and immunohistologically studied with the aim to identify possible neuronal cytoskeletal abnormalities. Results were compared to changes of substantia nigra reported in other conditions such as Parkinson's disease (PD) and methyl-4-phenylpyridine (MPTP) experimental toxicity. Three different substantia nigra neuronal types were observed. Morphological changes during aging consisted of distorted profile of the cell body and swelling and beading of dendritic branches. The quantitative assessment of changes observed in neuronal types showed a significant loss of dendrites and dendritic spines, especially in the oldest cases. These findings were similar to those previously described in other cerebral areas during aging, but a specific vulnerability of the largest substantia nigra neuronal type could be observed. Nodulations and beaded aspects of dendrites are reminiscent of those changes previously described in MPTP toxicity. Dendritic varicosities found in the oldest cases have also been found in dendrites of large substantia nigra neurons in PD. Cytoskeletal abnormalities have been described in PD but were not found in the present study. Therefore, other pathophysiological mechanisms different from the cytoskeletal compromise occurring in some neurodegenerative diseases should be involved in aging.
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PMID:Neuronal changes in the substantia nigra with aging: a Golgi study. 781 82

The locus coeruleus (LC) of eight adults without neurodegenerative disease and eight patients with Parkinson's disease was investigated by means of the Golgi-Braitenberg method for formalin-fixed human autopsy material. As with Golgi studies in the rat and cat, two main neuronal classes could be demonstrated in the human LC: (i) medium-sized fusiform and multipolar LC neurons known to contain neuromelanin and (ii) smaller neurons of widely varying somatic shape and dendritic arborization which are considered to be intermingled neurons of adjacent brain stem nuclei not containing neuromelanin. In Parkinson's disease, the Golgi-impregnated medium-sized LC neurons were reduced in number. They showed marked reduction of dendritic length, severe loss of spines, dendritic varicosities and swollen perikarya. The last two findings could be due in part to Lewy-body inclusions. The smaller non-noradrenergic neurons did not show severe pathological changes by the Golgi impregnation technique, which is in line with the fact that only neuromelanin-containing LC neurons are affected in the pathological process of Parkinson's disease.
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PMID:A Golgi study of human locus coeruleus in normal brains and in Parkinson's disease. 812 44

The aim of the present study was to determine whether the retrorubral nucleus projects to the dopaminergic nuclei in the ventral midbrain of the cat. For this purpose, injections of biotinylated dextran-amine or Phaseolus vulgaris-leucoagglutinin were placed into the retrorubral nucleus under stereotaxic guidance. The tracers were visualized by means of (immuno) histochemical procedures. In addition, tyrosine hydroxylase immunohistochemistry was used to evaluate the location of the injection sites and the distribution of the anterogradely labeled fibers. Both tracers reveal the same topography of labeled fibers in the ventral mesencephalon. Labeled fibers with varicosities were found ipsilaterally in the substantia nigra pars compacta, the substantia nigra pars lateralis, the ventral tegmental area and, contralaterally, in the substantia nigra pars compacta, the ventral tegmental area, and the retrorubral nucleus. A considerable number of labeled axons with varicosities were observed to be wrapped around the dendrites and perikarya of tyrosine hydroxylase-positive neurons in these areas. The present results are discussed in view of the possible role of the A8 dopaminergic cell group in the coordination of A9 nigrostriatal and A10 mesolimbic systems, as well as in the progressive pathology seen in patients suffering from Parkinson's disease.
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PMID:Efferent projections of the retrorubral nucleus to the substantia nigra and ventral tegmental area in cats as shown by anterograde tracing. 873 84

Interneuronal communication in the central nervous system (CNS) have always been of basic importance for theories on the cerebral morphofunctional architecture. Our group has proposed that intercellular communication in the brain can be grouped into 2 broad classes based on some general features of the transmission: wiring (WT) and volume (VT) transmission. WT occurs via a relatively constrained cellular chain (wire), while VT consists of 3-dimensional diffusion of signals in the extracellular fluid (ECF) for distances larger than the synaptic cleft. Both morphological and functional evidence indicates that dopamine (DA) synapses in striatum are 'open' synapses, i.e., synapses which favor diffusion of the transmitter into the surrounding ECF and observations are compatible with the view that DA varicosities can synthesize, store and release DA for VT. The DAergic mesostriatal transmission has, therefore, been examined by several groups to give experimental support to VT. Moreover, due to its minor structural requirements, VT may become prevalent under some pathological conditions, e. g. Parkinson's disease. In animal models of DAergic pathway degeneration, it has been shown that a compensatory activation of surviving DA terminals may lead to a preferential potentiation of VT. WT and VT favor different and complementary types of computation. VT is markedly slower and less safe than WT, but has minor spatial constraints and allows the reach of a large number of targets. Models of neuronal systems integrating classical neuronal circuits and diffusible signals begin to show how WT and VT may interact in the neural tissue.
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PMID:The emergence of the volume transmission concept. 965 6

The catecholamine precursor l-dihydroxyphenylalanine (L-DOPA) is the primary therapeutic intervention for Parkinson's disease. Although short-term exposure (30 min) potentiates dopamine (DA) release by elevating quantal size, longer term exposure to L-DOPA (48 hr) promotes neurite outgrowth from midbrain DA neurons in culture. To characterize long term effects of L-DOPA, we used a pheochromocytoma (PC12) line that extends neurites on exposure to nerve growth factor (NGF). L-DOPA potentiated the outgrowth of processes elicited by NGF. This response did not require conversion of L-DOPA to DA, was not caused by agonist effects at DA receptors, and was not blocked by the tyrosine kinase inhibitor genistein. However, similar results were found after exposure to l-n-acetylcysteine or apomorphine, a DA receptor agonist that produces a quinone metabolite, and seemed to correlate with glutathione synthesis. Long-term process elaboration was blocked by L-buthionine sulfoximine, consistent with mediation by an antioxidant mechanism. L-DOPA potentiation of NGF response was important functionally as seen by increased quantal neurotransmitter release from the L-DOPA/NGF-treated neurite varicosities, which displayed both 2-fold greater quantal size and frequency of quantal release. These results demonstrate potentiation by L-DOPA of morphological and physiological responses to neurotrophic factors as well as synergistic induction of antioxidant pathways. Together with effects on transmitter synthesis, these properties seem to provide a basis for the compound's long term presynaptic potentiation of DA release and therapeutic actions.
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PMID:A synergistic neurotrophic response to l-dihydroxyphenylalanine and nerve growth factor. 976 11

In contrast to the well-established dopaminergic innervation of the neostriatum, the existence of dopaminergic innervation of the subthalamic nucleus and globus pallidus is controversial. In the present study, tyrosine hydroxylase (TH)-immunoreactive elements were observed by light microscopy after antigen retrieval in the subthalamic nucleus and in the internal and external segments of the globus pallidus in postmortem human brain. Small islands of apparent neostriatal tissue with abundant arborization of fine, TH-immunoreactive axons in the vicinity of calbindin-positive small neurons resembling neostriatal medium spiny neurons were present in the external segment of the globus pallidus. Large numbers of medium-large, TH-immunoreactive axons were observed passing above and through the subthalamic nucleus and through both pallidal segments; these are presumed to be axons of passage on their way to the neostriatum. In addition, fine, TH-immunoreactive axons with meandering courses, occasional branches, and irregular outlines, morphologically suggestive of terminal axon arborizations with varicosities, were seen in both pallidal segments, including the ventral pallidum, and the subthalamic nucleus, consistent with a catecholaminergic (probably dopaminergic) innervation of these nuclei. This finding suggests that, in Parkinson's disease and in animal models of this disorder, loss of dopaminergic innervation might contribute to abnormal neuronal activation in these three nuclei.
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PMID:Tyrosine hydroxylase-immunoreactive elements in the human globus pallidus and subthalamic nucleus. 1037 26

Oxidant stress has been implicated in the pathogenesis of Parkinson's disease. To test the oxidant stress hypothesis of dopaminergic degeneration, age-related changes in the mesostriatal dopamine neuron system were compared between zitter mutant rats which have abnormal metabolism of oxygen species in the brain and Sprague-Dawley rat as a control using the neurochemistry and immunohistochemistry. Dopamine content in the caudate-putamen, nucleus accumbens and olfactory tubercle of zitter rats decreased significantly with age, and was lower than that found in corresponding age-matched controls. In the zitter rats, the reduction of dopamine was more prominent in the caudate-putamen than in the nucleus accumbens and olfactory tubercle. A characteristic decline of tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen of the zitter rat was also observed. In the dorsolateral caudate-putamen, reduction of tyrosine hydroxylase-immunoreactive fibers was observed in the matrix-like area, whereas in the ventromedial caudate-putamen the reduction occurred in the patch-like areas. Degeneration of tyrosine hydroxylase-immunoreactive fibers which was characterized by swollen varicosities and clustered fibers was observed in the caudate-putamen and nucleus accumbens and preceded loss of normal tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen. Thus, the depletion of dopamine in the terminal areas is related to axonal degeneration. However, there was no degenerative tyrosine hydroxylase-immunoreactive fibers in the olfactory tubercle at any examined age, but reductions of tyrosine hydroxylase-immunoreactive fibers and dopamine contents were noted in the olfactory tubercle after four months-of-age. Since the zitter rats have an abnormal oxygen metabolism, the degeneration of tyrosine hydroxylase-immunoreactive fibers could result from an accumulation of superoxide species. The present results provide support for the oxidant stress hypothesis of dopaminergic neuronal degeneration and further indicate the region-specific vulnerability of the nigrostriatal dopamine system.
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PMID:Age-related dopamine deficiency in the mesostriatal dopamine system of zitter mutant rats: regional fiber vulnerability in the striatum and the olfactory tubercle. 1065 18


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