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)

Regional loss of immunohistochemically identified neurons in serial sections through the brainstem of 4 patients with idiopathic Parkinson's disease was compared with equivalent sections from 4 age-matched control subjects. In the Parkinson brains, the catecholamine cell groups of the midbrain, pons, and medulla showed variable neuropathological changes. All dopaminergic nuclei were variably affected, but were most severely affected in the caudal, central substantia nigra. The pontine noradrenergic locus ceruleus showed variable degrees of degeneration. There was also a substantial loss of substance P-containing neurons in the pedunculopontine tegmental nucleus. However, the most severely affected cell group in the pons was the serotonin-synthesizing neurons in the median raphe. In the medulla, substantial neuronal loss was found in several diverse cell groups including the adrenaline-synthesizing and neuropeptide Y-containing neurons in the rostral ventrolateral medulla, the serotonin-synthesizing neurons in the raphe obscurus nucleus, the substance P-containing neurons in the lateral reticular formation, as well as the substance P-containing neurons in the dorsal motor vagal nucleus. Lewy bodies were present in immunohistochemically identified neurons in many of these regions, indicating that they were affected directly by the disease process. These widespread but region- and transmitter-specific changes help account for the diversity of motor, cognitive, and autonomic manifestations of Parkinson's disease.
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PMID:Neuropathology of immunohistochemically identified brainstem neurons in Parkinson's disease. 197 19

The levels in lumbar cerebrospinal fluid (CSF) of neuropeptide Y (NPY), methionine enkephalin (Enk), and Enk contained in amino- and carboxy-terminus extended forms (X-Enk) were examined in nine control patients undergoing elective surgical procedures and in eight patients with advanced Parkinson's disease, before and after the autologous transplantation of adrenal medullary fragments into the right caudate nucleus. The levels of CSF Enk and X-Enk before surgery in patients with Parkinson's disease were significantly less than those observed in control patients (Enk, 166 +/- 38 vs 264 +/- 44 pg/ml; X-Enk, 794 +/- 416 vs 1497 +/- 153 pg/ml). NPY levels did not differ (221 +/- 25 vs 193 +/- 23 pg/ml). After surgery, lumbar CSF samples were taken at 6 weeks, 12 weeks, 6 months, and 9 months. Placement of adrenal medullary fragments into the striatum had no effect on the levels of NPY or Enk at any time point. The levels of X-Enk were significantly enhanced only at 12 weeks (1138 +/- 140 pg/ml) but were at presurgical levels again by 6 months. These data suggest that the transplant was not functionally contributing to the CSF levels of these peptides.
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PMID:Measurement of lumbar CSF levels of met-enkephalin, encrypted met-enkephalin, and neuropeptide Y in normal patients and in patients with Parkinson's disease before and after autologous transplantation of adrenal medulla into the caudate nucleus. 231 64

1. The application of in situ hybridization histochemistry to the study of neuropeptide gene expression in human brain postmortem tissues is reviewed. We focus on neuropeptides preferentially expressed in hypothalamus and basal ganglia. 32P-labeled oligonucleotides were used as hybridization probes. 2. Autoradiography combined with computerized image analysis was used to visualize and quantify the hybridization signal. 3. Several criteria were considered in order to ascertain the specificity of the signal, including Northern analysis, use of heterologous probes, competition assays, and thermal stability of the hybrids. 4. In control human striatum high levels of hybridization signal were observed for somatostatin, neuropeptide Y, and preproenkephalin A mRNAs. In contrast, no detectable signal was observed with the cholecystokinin, arginine-vasopressin, and oxytocin probes in this area. In the hypothalamus high levels of oxytocin and arginine-vasopressin mRNAs were visualized in several nuclei. Preproenkephalin A and somatostatin mRNAs were also observed in this region, while cholecystokinin mRNA was not detected. 5. No significant correlations were found between the density of the hybridization signal and parameters such as postmortem delay, age, and gender in the population studied. 6. Finally, alterations of mRNA levels for some of these peptides were found in Parkinson's disease and Huntington's chorea striatal tissues. 7. These results show that in situ hybridization histochemistry can be used to examine at the microscopic level neuropeptide gene expression in postmortem materials.
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PMID:The use of in situ hybridization histochemistry for the study of neuropeptide gene expression in the human brain. 233 44

Neurochemical studies of post-mortem human parkinsonian brains have demonstrated specific alterations in neuropeptide concentrations within the substantia nigra and striatal structures. The drug, 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP) has been reported to act as a selective toxin to nigrostriatal dopamine neurons, and induces a parkinsonian-like syndrome in primates. In this study, marmosets developed features typical of Parkinson's disease following treatment with MPTP for four days. The effects of MPTP treatment on the concentrations of dopamine and neuropeptides were determined and changes compared with those reported for Parkinson's disease. It was found that within the substantia nigra, substance P concentrations doubled following treatment with MPTP; in contrast, concentrations of vasoactive intestinal peptide and neuropeptide Y were significantly reduced. No changes were observed in the concentrations of six other neuropeptides measured in this region, notably cholecystokinin. Despite marked depletion of dopamine within the caudate nucleus and putamen, concentrations of all neuropeptides within these structures remained unchanged with the exception of an isolated reduction of neuropeptide Y within the putamen. Somatostatin concentrations within the frontal cortex and hippocampus were significantly elevated in the marmosets treated with MPTP. These neuropeptide changes in the CNS contrast with those reported for Parkinson's disease. In view of the autonomic dysfunction associated with Parkinson's disease, peripheral concentrations of neuropeptides were determined. Significant depletion of neuropeptide Y was identified in the ureter, adrenal and cardiovascular tissue. Thus the neurochemical changes induced by MPTP may not be as selective as previously reported.
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PMID:Neuropeptides and dopamine in the marmoset. Effect of treatment with 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP): an animal model for Parkinson's disease? 241 54

The concentration of neuropeptide Y has been determined in the cortex and hippocampus of subjects with Parkinson's disease and compared to changes of activity of dopamine beta-hydroxylase and concentration of somatostatin. Despite a marked reduction in the concentration of somatostatin in the severely demented subject, in both cortex and hippocampus, no significant change in concentration of NPY was found in either region. This finding therefore suggests that the majority of NPY within the cortex is independent of somatostatin. This study provides some further evidence of neurochemical similarities between the dementia of Parkinson's disease and Alzheimer's disease.
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PMID:Dissociation of neuropeptide Y and somatostatin in Parkinson's disease. 286 Sep 55

Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in postmortem brain tissue from 12 control patients and 13 demented Parkinsonian patients who had Alzheimer-type cortical pathology. Twenty-two cortical regions were examined. Significant reductions in cortical SLI were found in 17 regions, while significant reductions in cortical NPYLI were found in nine regions. The reductions in SLI were typically 50-60%, while NPYLI reductions were 20-30%. These findings are similar to those in Alzheimer's disease (AD) and are consistent with a previous report of a dissociation between reductions in SLI and NPYLI in Parkinson's disease (PD) with dementia.
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PMID:Somatostatin and neuropeptide Y immunoreactivity in Parkinson's disease dementia with Alzheimer's changes. 290 67

Neuropeptides are widely distributed in the central nervous system, where they serve as neuroregulators. Recent interest has focused on their role in degenerative neurological diseases. We describe the normal anatomy of neuropeptides in both the cerebral cortex and basal ganglia as a framework for interpreting neuropeptide alterations in Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease. Concentrations of cortical somatostatin are reduced in AD and in dementia associated with Parkinson's disease. Concentrations of neuropeptide Y and corticotropin-releasing factor are also reduced in AD cerebral cortex. The reduced cortical concentrations of somatostatin and neuropeptide Y in AD cerebral cortex may reflect a loss of neurons or terminals in which these two peptides are co-localized. In Huntington's disease, basal ganglia neurons in which somatostatin and neuropeptide Y are co-localized are selectively preserved. Cerebrospinal fluid concentrations of neuropeptides in AD reflect alterations in cortical concentrations. Improved understanding of neuropeptides in degenerative neurological illnesses will help define which neuronal populations are specifically vulnerable to the pathological processes, and this could lead to improved therapy.
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PMID:Neuropeptides in neurological disease. 294 36

This paper provides an overview of the anatomical and functional organization of the most prominent chemospecific neuronal systems that compose the basal ganglia in primates. Emphasis is placed on the heterogeneity and diversity of small-molecule transmitters, neuroactive peptides and proteins used by basal ganglia neurons. Dopaminergic, serotoninergic and cholinergic neuronal systems are shown to comprise multiple subsystems organized according to highly specific patterns. These subsystems differentially regulate gene expression of several neuroactive peptides, including tachykinins, enkephalins, dynorphin, somatostatin, and neuropeptide Y, that are used by distinct subsets of basal ganglia neurons. Glutamatergic excitatory inputs establish distinct functional territories within the basal ganglia, and neurons in each of these territories act upon other brain neuronal systems through a GABAergic disinhibitory output mechanism. A striking complementary pattern of distribution of the calcium-binding proteins parvalbumin and calbindin D-28k is noted in all basal ganglia components. The limbic system-associated membrane protein (LAMP) is confined chiefly to basal ganglia sectors that are anatomically and functionally related to limbic system structures; these may serve as functional interfaces between the basal ganglia and the limbic system. The functional status of the various basal ganglia chemospecific systems in neurodegenerative diseases, such as Parkinson's disease and Huntington's chorea, is examined. It is concluded that these multiple transmitter-related systems cannot be analyzed separately as they form highly complex and interactive neuronal networks. These complexities should be taken into account to reach a better understanding of the functions of primate basal ganglia in health and disease.
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PMID:Chemical anatomy of primate basal ganglia. 756 12

The present study sought to determine whether the D1 dopamine receptor agonist CY 208-243 increases Fos-like immunoreactivity in neurochemically distinct populations of interneurons in the 6-hydroxydopamine-denervated striatum. In vivo microdialysis studies indicate that cholinergic interneurons in the striatum are excited by the administration of CY 208-243 and that this effect is potentiated by dopaminergic deafferentation. Since Fos is considered to be a marker of neuronal activity, we examined the overlap between CY-208-243-induced Fos-like immunoreactivity and striatal cholinergic interneurons labelled with the cholinergic marker enzyme choline acetyltransferase. Unexpectedly, cholinergic interneurons in the striatum were not found to express Fos-like immunoreactivity. However, D1 agonist-induced Fos-like immunoreactivity was found in neurons immunoreactive for neuropeptide Y. Consequently, the failure of cholinergic neurons in the striatum to express D1 agonist-induced Fos-like immunoreactivity does not appear to be a general property of striatal interneurons. Indeed, CY 208-243 increased Fos-like immunoreactivity in choline-acetyltransferase-positive neurons in the basal forebrain and lateral dorsal tegmental nucleus. In the case of cholinergic basal forebrain neurons, administration of CY 208-243 has been shown to enhance the release of acetylcholine from their terminals located in the frontal cortex. Thus, unlike cholinergic interneurons in the striatum, the expression of Fos-like immunoreactivity in cholinergic basal forebrain neurons is correlated with an increase in transmitter release. Choline acetyltransferase immunoreactivity was markedly reduced in cholinergic basal forebrain neurons ipsilateral to the 6-hydroxydopamine lesion. This decrease in choline acetyltransferase immunoreactivity was confined to a pocket of cortically projecting neurons located in the posterior part of the horizontal limb of the diagonal band which included the medial preoptic nucleus. Interestingly, D1 agonist-induced Fos-like immunoreactivity was located predominantly in those cholinergic neurons which displayed depressed choline acetyltransferase immunoreactivity. Since Fos is often induced as a consequence of increased activity, it is tempting to speculate that those neurons which stained weakly for choline acetyltransferase had been excited by the D1 agonist administration. Accordingly, the destruction of mesencephalic dopaminergic neurons with 6-hydroxydopamine may have deprived these cholinergic neurons of an excitatory D1 receptor-mediated drive, resulting in a reduction of choline acetyltransferase immunoreactivity. These results suggest that the degeneration of nigrostriatal dopamine neurons may contribute to the loss of cholinergic basal forebrain function in Parkinson's disease.
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PMID:D1 dopamine receptor agonist-induced Fos-like immunoreactivity occurs in basal forebrain and mesopontine tegmentum cholinergic neurons and striatal neurons immunoreactive for neuropeptide Y. 791 82

Electroconvulsive therapy (ECT) was given to 16 non-depressed, non-demented patients with advanced Parkinson's disease (PD). In all the patients an antiparkinsonian effect was seen, lasting for 18 months in one patient, 3-5 months in seven patients, and a few days to four weeks in eight patients. After ECT the levels of homovanillic acid and neuropeptide Y in cerebrospinal fluid (CSF) were significantly increased. The eight patients with long lasting motor improvement after ECT had significantly lower CSF-3-methoxy-4-hydroxyphenylglycol compared to the group with short lasting improvement. Five patients developed transitory mental confusion after ECT. In these patients, and in no others, a high albumin-ratio was found already before ECT was given - an indication of blood CSF barrier damage. Our results suggest that ECT is valuable in patients with drug refractory PD or PD with intolerance to antiparkinsonian drugs.
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PMID:ECT in Parkinson's disease. Changes in motor symptoms, monoamine metabolites and neuropeptides. 962 60


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