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)

In-vivo microdialysis has been used extensively to study the neurochemical mechanisms of ischemia, epilepsy and hypoglycemia. It is also being increasingly used to document the response of neurons to various medications. Most of the work to date has been done in small animals. In the last 2 years, the technique has been adapted for use in patients with subarachnoid hemorrhage, head trauma, Parkinson's disease, brain tumors and epilepsy. Two of the major limiting factors are the invasiveness of the technique and the resultant potential for CNS infection. We describe a simple, safe and reliable method to measure neurochemical changes in the human brain with in-vivo microdialysis. We were able to easily monitor for 4-6 h daily for up to 4 days in awake or comatose patients with subarachnoid hemorrhage or head trauma. Cerebral concentrations of glutamate, GABA, other amino acids and catecholamines were measured. This technique thus has a potential for on-line measurements of neurotoxins in patients with unstable neurological conditions.
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PMID:A new method of in-vivo microdialysis of the human brain. 854 74

An ATP-sensitive potassium channel (KATP) is known to modulate insulin release from pancreatic beta cells. It has been proposed that potassium channels related to KATP in the nervous system might similarly modulate neurotransmitter release. We have therefore investigated the effects of KATP opening agents on GABA release in the globus pallidus. Diazoxide and cromakalim decreased the K(+)-evoked release of [3H]GABA from pallidal slices. The maximum inhibition observed for diazoxide (59%) and cromakalim (66%) was achieved at a concentration of 100 microM. The effects of both cromakalim and diazoxide were significantly antagonized by the concurrent application of the sulfonylurea glibenclamide (100 microM). Intrapallidal injections of diazoxide in the reserpine-treated rat model of Parkinson's disease reduced akinesia in a dose-dependent manner. These data suggest that manipulation of neuronal potassium channels with pharmacological properties similar to KATP may prove useful in the treatment of Parkinson's disease.
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PMID:Modulation of GABA transmission by diazoxide and cromakalim in the globus pallidus: implications for the treatment of Parkinson's disease. 863 58

The distribution, molecular structure and role of adenosine A2 receptors in the nervous system, is reviewed. The adenosine A2a receptor subtype, identified in the nervous system with ligand binding, functional studies or genetic molecular techniques, has been demonstrated in the striatum and other basal ganglia structures, in the hippocampus, in the cerebral cortex, in the nucleus tractus solitarius, in motor nerve terminals, in noradrenergic terminals in the vas deferens, in myenteric neurones of the ileum, in the retina and in the carotid body. The A2b receptors have been identified in glial and neuronal cells, and may have a widespread distribution in the brain. Activation of adenosine A2a receptors can enhance the release of several neurotransmitters, such as acetylcholine, glutamate, and noradrenaline. The release of GABA might be either enhanced or inhibited by A2a receptor activation. The A2 receptor activation also modulates neuronal excitability, synaptic plasticity, as well as locomotor activity and behaviour. The ability of A2 receptors to interact with other receptors for neurotransmitters/neuromodulators, such as dopamine D2 and D1 receptors, adenosine A1 receptors, CGRP receptors, metabotropic glutamate receptors and nicotinic autofacilitatory receptors, expands the range of possibilities used by adenosine to interfere with neuronal function and communication. These A2 receptor-mediated adenosine actions might have potential therapeutic interest, in particular in movement disorders such as Parkinson's disease and Huntington's chorea, as well as in schizophrenia, Alzheimer's disease, myasthenia gravis and myasthenic syndromes.
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PMID:Adenosine A2 receptor-mediated excitatory actions on the nervous system. 873 76

Cerebrospinal fluid (CSF) samples from patients undergoing lumbar puncture for suspected neurological diseases were fractioned into macromolecular (MW > 3000 Daltons) and small molecule components (MW < 3000 Daltons). The macromolecular component was tested for its interference with GABA stimulation of 36Cl- accumulation in rat cerebral cortex microsacs. For many pathologies, no interference was apparent; an exception was two patients with Parkinson's disease in whom there were clear signs of stimulated GABA activity. This last result seems worthy of further investigation.
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PMID:Screening of the macromolecular component of CSF from various pathologies for its interference with GABAA receptor function. 883 91

Exposure to elevated levels of Manganese (Mn) can result in an irreversible brain disease characterized by extrapyramidal signs and symptoms resembling Parkinson's disease. To identify the neuronal target of Mn neurotoxicity, MnCl2 was added to serumless dissociated mesencephalic-striatal cultures from rat embryo on day 4 in vitro. High affinity 3H-dopamine (DA) and 14C-GABA uptakes were assessed as specific functional markers of DAergic and GABAergic cell viability, respectively. After 60-min exposure, MnCl2 at 0-200 microM did not modify the morphologic appearance of the cultures, specific DA and GABA uptakes, or the number of DA neurons visualized by immuno-cytochemical staining with tyrosine hydroxylase. In contrast, culture exposure to 20 microM MnCl2 for 24 h selectively reduced specific GABA uptake without affecting specific DA uptake or the number of DA neurons. The exposure to a higher MnCl2 concentration was accompanied by signs of general toxicity. Striatal GABA neurons seemed to be more susceptible to Mn toxicity than mesencephalic GABA neurons. Overall, our data suggest that striatal neurons rather than mesencephalic DA neurons may be the main target of Mn neurotoxicity.
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PMID:Manganese toxicity in serumless dissociated mesencephalic and striatal primary culture. 884 9

One of the primary approaches in experimental brain research is to investigate the effects of specific destruction of its parts. Here, several neurotoxins are available which can be used to eliminate neurons of a certain neurochemical type or family. With respect to the study of dopamine neurons in the brain, especially within the basal ganglia, the neurotoxin 6-hydroxydopamine (6-OHDA) provides an important tool. The most common version of lesion induced with this toxin is the unilateral lesion placed in the area of mesencephalic dopamine somata or their ascending fibers, which leads to a lateralized loss of striatal dopamine. This approach has contributed to neuroscientific knowledge at the basic and clinical levels, since it has been used to clarify the neuroanatomy, neurochemistry, and electrophysiology of mesencephalic dopamine neurons and their relationships with the basal ganglia. Furthermore, unilateral 6-OHDA lesions have been used to investigate the role of these dopamine neurons with respect to behavior, and to examine the brain's capacity to recover from or compensate for specific neurochemical depletions. Finally, in clinically-oriented research, the lesion has been used to model aspects of Parkinson's disease, a human neurodegenerative disease which is neuronally characterized by a severe loss of the meso-striatal dopamine neurons. In the present review, which is the first of two, the lesion's effects on physiological parameters are being dealt with, including histological manifestations, effects on dopaminergic measures, other neurotransmitters (e.g. GABA, acetylcholine, glutamate), neuromodulators (e.g. neuropeptides, neurotrophins), electrophysiological activity, and measures of energy consumption. The findings are being discussed especially in relation to time after lesion and in relation to lesion severeness, that is, the differential role of total versus partial depletions of dopamine and the possible mechanisms of compensation. Finally, the advantages and possible drawbacks of such a lateralized lesion model are discussed.
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PMID:Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae. 887 4

We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in plasma), asparagine, glutamine, glycine and GABA in 31 patients with Parkinson's disease and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had similar CSF levels of glutamate, glutamine, asparagine, and glycine higher CSF GABA levels higher plasma levels of glutamine, asparagine, and glycine, and lower plasma levels of aspartate. The CSF levels of the amino acids measured were not correlated with the clinical features of PD. Our results that CSF GABA levels are not decreased in PD as previously suggested.
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PMID:Neurotransmitter amino acids in cerebrospinal fluid of patients with Parkinson's disease. 888 Jun 90

A model of basal ganglia functioning proposed a few years ago suggests that increased and decreased activity in basal ganglia output to the thalamus underlies akinesia, as seen in Parkinson's disease, and dyskinetic movements as seen in Huntington's disease or after treatment with L-dopa and neuroleptics, respectively. Although the basic features of this model have stood the test of time, patterns of electrophysiological activity and changes in indices of GABA-dependent transmission in the external pallidum lead to a reconsideration of the mechanisms responsible for these changes in output activity.
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PMID:Basal ganglia and movement disorders: an update. 910 54

L-DOPA is proposed to be a neurotransmitter and/or neuromodulator in CNS. It is released probably from neurons, which may contain L-DOPA as an end-product, and/or from some compartment other than catecholamine-containing vesicles. The L-DOPA itself produces presynaptic and postsynaptic responses. All are stereoselective and most are antagonized by competitive antagonist. In striatum, L-DOPA is neuromodulator, mother of catecholamines, not only a precursor for dopamine but also a potentiator of children for presynaptic beta-adrenoceptors to facilitate dopamine release and postsynaptic D2 receptors, and ACh release inhibitor. All may cooperate for Parkinson's disease. Meanwhile, supersensitization of increase in L-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or "on-off" during chronic therapy. In lower brainstem, L-DOPA tonically activates postsynaptic depressor sites of NTS and CVLM and pressor sites of RVLM. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in NTS. GABA, the inhibitory neuromodulator for baroreflex in NTS, tonically functions to inhibit, via GABAA receptors, L-DOPA release and depressor responses to levodopa. Levodopa inversely releases GABA. L-DOPAergic monosynaptic relay from NTS to CVLM and from PHN to RVLM is suggested. Tonic L-DOPAergic baroreceptor-aortic nerve-NTS-CVLM relay seems to carry baroreflex information. Disturbance of neuronal activity to release L-DOPA in NTS, loss of the activity in CVLM, enhancement of the activity with decreased decarboxylation and increase in sensitivity to levodopa in RVLM may be involved in maintenance of hypertension in SHR. This is a story of "L-DOPAergic receptors" with extremely high affinity and low density.
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PMID:Neurobiology of L-DOPAergic systems. 889 95

Hyperexcitable reflex blinks are a cardinal sign of Parkinson's disease. We investigated the neural circuit through which a loss of dopamine in the substantia nigra pars compacta (SNc) leads to increased reflex blink excitability. Through its inhibitory inputs to the thalamus, the basal ganglia could modulate the brainstem reflex blink circuits via descending cortical projections. Alternatively, with its inhibitory input to the superior colliculus, the basal ganglia could regulate brainstem reflex blink circuits via tecto-reticular projections. Our study demonstrated that the basal ganglia utilizes its GABAergic input to the superior colliculus to modulate reflex blinks. In rats with previous unilateral 6-hydroxydopamine (6-OHDA) lesions of the dopamine neurons of the SNc, we found that microinjections of bicuculline, a GABA antagonist, into the superior colliculus of both alert and anesthetized rats eliminated the reflex blink hyperexcitability associated with dopamine depletion. In normal, alert rats, decreasing the basal ganglia output to the superior colliculus by injecting muscimol, a GABA agonist, into the substantia nigra pars reticulata (SNr) markedly reduced blink amplitude. Finally, brief trains of microstimulation to the superior colliculus reduced blink amplitude. Histological analysis revealed that effective muscimol microinjection and microstimulation sites in the superior colliculus overlapped the nigrotectal projection from the basal ganglia. These data support models of Parkinsonian symtomatology that rely on changes in the inhibitory drive from basal ganglia output structures. Moreover, they support a model of Parkinsonian reflex blink hyper-excitability in which the SNr-SC target projection is critical.
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PMID:An explanation for reflex blink hyperexcitability in Parkinson's disease. I. Superior colliculus. 892 37


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