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

The neurotransmitter dopamine has biological attributes that make it amenable to study by positron emission tomography, unlike many of the 40 or so neurotransmitters that have been identified in the brain. Dopamine deficiency in the nigrostriatal system is a characteristic of Parkinson's disease, and a disturbance of dopamine metabolism is still widely held to be responsible for the syndrome of schizophrenia. Despite its importance in the regulation of locomotion and mood, it has been impossible to visualize the intracerebral distribution of dopamine and measure its regional metabolism in man. In the first demonstration of the regional distribution of a neurotransmitter in the brain of conscious normal man, we show here that L-3,4-dihydroxyphenylalanine (L-dopa) labelled in the 6-position with the positron-emitting radionuclide fluorine-18, localizes specifically in the dopaminergic pathways of the human brain where its turnover could be measured atraumatically by positron emission tomography.
 ...
PMID:Dopamine visualized in the basal ganglia of living man. 660 27

The nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex, was morphometrically investigated in 58 cases of neuropsychiatric disorders and compared to 14 controls. The results demonstrate a loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease (70%), paralysis agitans (77%), and Korsakoff's disease (47%) but no marked reduction of neurons in postencephalitic parkinsonism, Huntington's disease, chronic alcoholism without dementia, schizophrenia and infantile brain damage. Neurons of the three subdivisions of the nucleus basalis of Meynert (the nucleus septi medialis, the nucleus of the diagonal band of Broca and the nucleus basalis Meynert neurons in the substantia innominata) may be affected in a different manner in different patients within a single group homogeneous with respect to the usual clinical and neuropathological diagnostic criteria. Cell loss in the basal forebrain is restricted to the large neurons of the nucleus basalis, the immediately adjacent neurons of the globus pallidus externus not being affected. The selective degeneration of these neurons provides the morphological correlate of the cortical cholinergic deficiency in these neuropathological conditions. The degeneration of this discrete cholinergic neuronal population in several disorders of higher cortical function is probably directly related to the progressive deterioration of memory and cognitive processes in affected patients.
 ...
PMID:Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease. 663 93

The normal postinfancy human brain contains microscopical structure referred to as the dense microsphere (DMS). The function and significance of the DMS are presently unknown. The light microscopical, topographical, histochemical and ultrastructural aspects of the DMS are described, based on the study of 106 normal and 50 diseased brains. The frequency of DMS in random samples of temporal neocortex was compared in 96 normals, 10 cases of Alzheimer's disease, 10 cases of Parkinson's disease, 10 cases of schizophrenia, and 20 cases of other nervous diseases. No significant differences were found between diagnostic categories but there was statistically significant reduction in frequency with ageing. These findings are discussed in relation to the possible significance of the DMS.
 ...
PMID:Dense microspheres in normal human brain. 663 99

A quantitative study of the melanin-containing dopaminergic neurons of the nigrostriatal system (A 9) and of the mesolimbic system (A 10) was carried out on Nissl-stained serial sections of nine normal brains, six age-matched brains of schizophrenics, five brains of paralysis agitans, and six brains of postencephalitic parkinsonism. By contrast with most laboratory animals the A 10 cell group is not well developed in the human brain. Both in Parkinson's disease with a known hypoactivity of dopamine neurons and in schizophrenia with a postulated hyperfunction of these systems, pathological alterations of the dopamine cell groups can be observed. In paralysis agitans the nigrostriatal and the mesolimbic cell groups exhibit a significant loss of neurons, while the remaining mesolimbic cells appear to be in better condition. In the postencephalitic parkinsonism both systems have almost completely disappeared with a significant loss of nerve and glial cells. In schizophrenia there is a significant decrease in the volume of the nigrostriatal area. Here the mean volume of the glial nuclei is reduced, whereas the mean volume of the nerve cells is diminished in the mesolimbic part.
 ...
PMID:A morphometric study of the dopamine-containing cell groups in the mesencephalon of normals, Parkinson patients, and schizophrenics. 664 8

Ungerstedt observed that the dopamine-containing innervation of the forebrain can be divided into two parts: a nigrostriatal system, originating mainly in the pars compacta of the substantia nigra and innervating the caudoputamen; and a mesolimbic system arising mainly in the ventral tegmental area and innervating the nucleus accumbens and olfactory tubercle. This classification has since been modified and extended with the discovery of the mesocortical dopamine system. The original distinction between nigrostriatal and mesolimbic systems nevertheless was pivotal in suggesting that the basal ganglia are related to limbic as well as to sensorimotor functions, and remains of interest because dopaminergic mechanisms may be implicated not only in the aetiology of sensorimotor impairments such as those of Parkinson's disease, but also in neuropsychiatric disorders such as schizophrenia. The striatal targets of the mesolimbic and nigrostriatal systems are now known to be distinct also in terms of forebrain connections, despite some overlap of fibre projections. The nucleus accumbens-olfactory tubercle region and abutting caudoputamen (together called the 'ventral' or 'limbic' striatum) are characteristically related to limbic parts of the forebrain, whereas the large remainder of the caudoputamen (the 'dorsal' or 'non-limbic' striatum) is most closely related to sensorimotor regions. We report here evidence that the mesolimbic and nigrostriatal systems are differentially affected in the mutant mouse weaver, and in particular that dopamine is severely depleted in the dorsal striatum of weaver but relatively spared in the ventral striatum. We conclude that dopamine-containing fibre systems innervating the limbic and non-limbic striatum can be influenced separately in genetic disease and that genetic control, whether direct or indirect, may be exerted at the single-gene level.
 ...
PMID:Weaver mutation has differential effects on the dopamine-containing innervation of the limbic and nonlimbic striatum. 669 Sep 83

The close relationship of cholecystokinin peptides with some of the dopamine pathways and the limbic system suggests a putative role for these peptides in the pathophysiology of neuropsychiatric disorders such as Parkinson's disease, manic-depression and schizophrenia. By use of radioimmunoassay, we report a significant decrease in cholecystokinin-immunoreactivity in the cerebrospinal fluid of patients with bipolar manic-depression and untreated schizophrenia in comparison to control subjects.
 ...
PMID:Reduced cholecystokinin immunoreactivity in the cerebrospinal fluid of patients with psychiatric disorders. 669 11

The capability of positron computed tomography (PCT) to delineate the substructures of the brain and its facility for accurately measuring the local tissue radioactivity concentration allow the application of tracer kinetic models for the study of local cerebral function in man. This principle and an adaptation of the 14C-deoxyglucose (DG) model of Sokoloff et al. with 18F-2-fluoro-deoxy-D-glucose (FDG) is being used at UCLA. Brookhaven National Laboratory, University of Pennsylvania, NIH, and the Massachusetts General Hospital to determine the local cerebral glucose metabolic rate (LCMRGIc) in normal man at rest and during sensory activation and the changes that occur in patients with a variety of cerebral disorders. Kinetic studies with PCT have been employed to measure the rate constants of the model in different gray and white matter structures of the brain in both normal and ischemic states. The precision of the method in normals has been shown to be about +/- 5% for 1.5-2.0 sq cm regions of the brain. Studies in normals have yielded values for hemispheric CMRGIc that are in agreement with measurement using the Kety-Schmidt technique and LCMRGIc values in agreement with values in monkeys using DG autoradiography. Studies in volunteers subjected to visual and auditory stimulation are demonstrating the potential of this technique for investigating the human brain's response to different stimuli. STudies in patients with stroke show excellent correlation between the degree, extent, and particular structures involved and the clinical symptoms. The method consistently detected hypometabolism in cortical, thalamic, and striatal tissues that were dysfunctional due to deactivation or damage but which appeared normal on x-ray CT. Studies in patients with partial epilepsy have shown hypometabolic zones that highly correlated anatomically with interictal EEG spike foci and were associated with normal x-ray CT studies in 77% of the patients studied. The studies on epilepsy at UCLA have resulted in the integration of the LCMRGIc study into the clinical workup of patients with partial epilepsy that are candidates for surgical resection of their epileptogenic focus (effective June 1979). Studies on Huntington's chorea, Parkinson's disease, aphasia, dementia, schizophrenia, and tumors are in early stage of investigation but also are providing exciting new results. Further studies are needed to determine the role of the local function information obtained with the PCT-FDG method in elucidating the basic mechanism and the potential to aid in improving the approach to medical therapy.
 ...
PMID:Positron computed tomography studies of cerebral glucose metabolism in man: theory and application in nuclear medicine. 697 94

Receptor binding studies with a variety of dopaminergic ligands have confirmed behavioral and biochemical findings that the central nervous system and peripheral nervous system contain several dopamine receptor subtypes. These subtypes can be discriminated on the basis of their agonist-antagonist pharmacological specificities, linkage to adenylate cyclase, cellular location, regulation by guanine neucleotides and ions, and involvement in several human diseases. Although questions remain unanswered, progress is rapidly being made in equating the subgroupings arrived at by these different experimental approaches. Dopamine receptors are regulated by a number of factors. Acutely, guanine nucleotides and some ions regulate agonist but not antagonist binding and are essential for receptor coupling with adenylate cyclase. Chronically, changes in the level of dopaminergic stimulation modulate the number of at least some receptor subtypes, resulting in "up or down regulation." An increase in receptor number appears central to the pathology of Parkinson's disease, tardive dyskinesia, and perhaps schizophrenia. Animal models indicate that it may be possible to exploit inherent capabilities for receptor modulation in clinical therapy. The therapeutic precedents set by the indentification of distinct subtypes of adrenoreceptors. histamine, and cholinergic receptors portends and exciting future for dopamine receptor research.
 ...
PMID:Dopamine receptors: subtypes, localization and regulation. 700 83

Focal microdegenerative changes in the nuclei of the ansa peduncularis and the septum pellucidum are present in most cases of presenile and senile dementia, Parkinson's disease and schizophrenia (7,8). These nuclei interconnect and have extensive synaptic connections with the areas of the brain recently shown to contain non-cytopathic reovirus antigen and reovirus-like particles in the normal adult (9,10). The reovirus-involved regions closely approximate the overall pattern of the topography of brain atrophy in Alzheimer's dementia and Parkinson's disease. Mechanisms are suggested whereby mutant defective reovirus present in all adult human brains is responsible or related to the major forms of chronic mental illness including the common types of dementia and schizophrenia.
 ...
PMID:Reovirus and the pathogenesis of some forms of chronic mental illness. 704 35

Pergolide mesylate is a potent dopamine agonist that is being evaluated clinically in Parkinson disease, hyperprolactinemia, and other diseases. Pergolide activates both presynaptic and postsynaptic dopamine receptors, with some apparent selectivity for the presynaptic dopamine autoreceptors. In rats, low doses of pergolide (0.01 mg/kg or less, intraperitoneally) decreased dopamine turnover in brain, decreased serum prolactin concentration, and reduced blood pressure in spontaneously hypertensive rats. At somewhat higher doses (0.05 mg/kg or more, intraperitoneally), pergolide caused contralateral turning in nigrostriatal-lesioned rats, elevation of serum corticosterone, and hypermotility with stereotyped behavior. All of these actions are thought to be due to stimulation of dopamine receptors at various sites, but the data suggest that pergolide may have preferential affinity for presynaptic dopamine receptors. If low doses of pergolide can reduce dopaminergic transmission by activating presynaptic receptors that control dopamine release, then this action might be therapeutically useful in treating schizophrenia without causing tardive dyskinesia or in the treatment of tardive dyskinesia. The long duration of action of pergolide seen in animal and human studies could be an important advantage over some other dopamine agonists such as apomorphine.
 ...
PMID:Degree of selectivity of pergolide as an agonist at presynaptic versus postsynaptic dopamine receptors: implications for prevention or treatment of tardive dyskinesia. 717 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>