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)

A public health network involves several and different health professionals who work in synergy to achieve a common objective: to improve the management of a given disease. Per se, this objective could not be achieved by each of these professionals if working separately. In practice, existing public health networks ensue from very different legal frameworks and come up against various impediments. They have been developed mainly for the management of chronic and serious diseases (e.g. asthma, diabetes, virus C hepatitis, Parkinson's disease, drug abuse). Public health networks can be a very valuable source of data for clinical and epidemiological research, mainly because patients are followed up over a very long period and information coming from various health professionals (general practitioners, specialists, nurses, etc.) is centralized and recorded in a common database. It can also be useful for pharmacovigilance purposes (assessment of Type A and delayed reactions). In any case, the relative interest of such networks should be regularly assessed by an ad hoc methodology, e.g. an experimental or pseudo-experimental design vs. a reference. Despite the fact that there are relatively few operational networks, they can be of great interest for clinical research.
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PMID:[Public health networks: practical aspects and contribution to clinical research. Round table no. 2. XV]. 1109 33

Dopaminergic neurons and their projection-systems are important in some fundamental human activities like locomotion, feeding and sex, essential for survival and procreation, and are relevant to pathologies like Parkinson's disease and drug abuse. Three main dopaminergic projection-systems, namely the nigrostriatal, mesocortical and mesolimbic pathways are the major targets of the neuropharmacological actions of psychomotor stimulants such as cocaine and amphetamine. Studies on knockout mice for dopamine or its receptors provide substantial information but fail to reveal the role of individual dopaminergic projection-systems. Mutant animals with defects specific to one or more projection-systems might be useful for studying the role of individual dopaminergic projection-systems. We propose the weaver mutant mouse, with a defective nigrostriatal dopaminergic projection-system and dopamine depletion in the dorsal striatum but with intact mesocorticolimbic projection-systems, as a suitable model to study the role of individual dopaminergic systems in diverse biological processes including Parkinson's disease and drug abuse.
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PMID:The weaver mutant mouse: a model to study the ontogeny of dopamine transmission systems and their role in drug addiction. 1124 Mar 9

The aim of the present experiment was to investigate the possibility that alterations in dopamine D3 receptors have a role in the normalization of function that occurs following a unilateral lesion of the medial forebrain bundle induced by 6-hydroxydopamine (6-OHDA). Unilateral lesions result in an enhanced rotational response to dopamine agonists that appears to be due to an increase in stimulatory D2 receptors on the lesioned side that occurs by about 1 week postlesion. The present experiment assessed the involvement of D3 receptors in rotational behavior by testing the animals at 48 h postlesion. At this time interval, D2 receptors have not become up-regulated. In contrast, D3 receptors have been shown to be down-regulated. Rats with > or = 98% dopamine depletion induced by 6-OHDA exhibited mostly ipsilateral rotation in response to an injection of amphetamine. This rotation was not affected by pretreatment with the D3 antagonist U-99194A. Rats with 80-97% dopamine depletion exhibited mostly contralateral rotation in response to amphetamine and this rotation was blocked by pretreatment with U-99194A. In addition, a decrease in D3 receptor binding was observed by 48 h postlesion. These results support the hypothesis that the decrease in D3 receptors seen following denervation is involved in the compensatory response of the system. This may have important clinical relevance in the treatment of disorders such as Parkinson's disease and drug abuse.
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PMID:Dopamine D3 receptors are involved in amphetamine-induced contralateral rotation in 6-OHDA lesioned rats. 1156 41

PET can map neurotransmitter synthesis, storage, release, binding to receptors, and re-uptake in the brain with tracer concentrations in the picomolar or nanomolar range. Tracers are analogues of naturally occurring precursors or ligands, or are drugs, which bind with varying degrees of specificity to receptor subtypes in the brain. Tracers have been synthesised for many transmitter systems, but dopaminergic and serotonergic neurotransmissions are the main foci of current efforts to selectively trace synthesis, storage, re-uptake, or post-synaptic binding of neurotransmitters. Common measures of the tracer uptake and binding include precursor clearance (k3), a measure of transmitter synthesis and trapping, and binding potential (pB), a measure of the receptor binding per unit of unbound tracer, and hence a measure of the release of the endogenous transmitter, or the occupancy of a drug. Dopamine tracers are used in diseases of the basal ganglia, whereas serotonin, benzodiazepine, and opiate tracers are used in lesions of the cerebral cortex. PET has revealed loss of dopaminergic terminals and dopamine synthetic capacity in Parkinson's disease, MPTP intoxication, and Lesch-Nyhan's syndrome; release of dopamine after administration of cocaine and amphetamine, and in motor activity and cognition; increased synaptic dopamine and release of dopamine, and the 70-90% neuroleptic occupancy of dopamine receptors in the striatum, in patients with schizophrenia; loss of muscarinic and nicotinergic receptors in Alzheimer's disease, and benzodiazepine and opiate receptors in stroke, epilepsy, and Huntington's chorea; altered opiate receptors in chronic pain and drug abuse; and release of opiates in analgesia; but changes in serotonin synthesis, transport, and binding in affective or psychotic disorders remain elusive.
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PMID:[Receptor mapping in living human beings by means of positron emission tomography]. 1157 27

Recent drug discovery programs aimed at identifying selective metabotropic mGlu receptor ligands by high-throughput functional screening efforts have revealed subtype-selective allosteric modulators of mGlu1 and mGlu5 receptors that are structurally unrelated to glutamate. In contrast to competitive ligands, which bind to the glutamate binding site located in the large N-terminal extracellular domain, these modulators act as non-competitive antagonists, inverse agonists or positive modulators by binding to specific residues in the seven-transmembrane domain. More recent studies to assess the potential of these compounds in in vivo models of nervous system disorders have implicated the mGlu5 receptor subtype as a potentially important therapeutic target for inflammatory pain, anxiety, Parkinson's disease and drug abuse, and mGlu1 and mGlu5 receptors as potential targets for anticonvulsant and neuroprotective therapies. Very recent findings indicate an important regulatory role for intracellular proteins interacting with metabotropic glutamate receptors, which might constitute novel drug targets for modulating metabotropic glutamate receptor activity.
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PMID:Allosteric modulators of group I metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives. 1178 7

The Bechara simulated gambling task is a popular method of examining decision-making deficits exhibited by people with brain damage, psychopathology, antisocial personality, or drug abuse problems. However, performance on this task is confounded by complex interdependencies between cognitive, motivational, and response processes, making it difficult to sort out and identify the specific processes responsible for the observed behavioral deficits. The authors compare 3 competing cognitive decision models of the Bechara task in terms of their ability to explain the performance deficits observed in Huntington's disease patients as compared with healthy populations and people with Parkinson's disease. The parameters of the best fitting model are used to decompose the observed performance deficit of the Huntington patients into cognitive, motivational, and response sources.
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PMID:A contribution of cognitive decision models to clinical assessment: decomposing performance on the Bechara gambling task. 1221 32

Alterations in dopaminergic system are known to lie in the basis of such diseases as Parkinson's disease, Huntington's disease, Attention Deficit/Hyperactivity Disorder, Tourette syndrome, schizophrenia and drug abuse. This induced broad investigations of dopaminergic system in nearly all the areas of neuroscience. New insights into the pathogenesis of neuropsychiatric diseases have emerged. Research in the field of dopaminergic neurotransmission and memory was awarded Nobel prize in the year 2000. New avenues for the development of more selective drugs have been opened. In their daily practice clinicians are often prescribing medications acting on presynaptic or postsynaptic sites of dopaminergic units. Thus the aim of this review was to renew some knowledge on the architecture of dopaminergic system and also to glance through some of the studies implying its modulating effect on cognitive functions.
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PMID:[Dopaminergic modulation of cerebral activity and cognitive functions]. 1247 82

Dopamine plays an important role in the working memory functions of the prefrontal cortex, functions that are impacted in age-related memory decline, drug abuse, and a wide variety of disorders, including schizophrenia and Parkinson's disease. We have previously reported that dopamine depresses excitatory transmission between pyramidal neurons in the prefrontal cortex. Here, using paired recordings, we have investigated dopaminergic modulation of excitatory transmission from pyramidal neurons to fast-spiking (FS) interneurons. In contrast to its effect on recurrent excitation, dopamine was without effect on excitatory transmission to FS interneurons. However, dopamine has directly enhanced the excitability of the FS interneurons to the extent that even a single excitatory postsynaptic potential could initiate spiking with great temporal precision in some of them. These results indicate that dopamine's effects on excitatory transmission are target-specific and that the axon terminals of pyramidal neurons can be selectively regulated at the level of individual synapses. Thus, dopamine's net inhibitory effect on cortical function is remarkably constrained by the nature of the microcircuit elements on which it acts.
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PMID:Selective modulation of excitatory and inhibitory microcircuits by dopamine. 1259 42

HIV-1 infection of the brain can lead to the development of clinical syndromes reminiscent of Parkinson's disease, suggesting that HIV infection may damage nigrostriatal dopamine (DA) neurons. Although the responsible mechanisms have not been well defined, neurotoxic viral proteins, such as Tat, released from infected cells may be involved. Drug abuse is a major risk factor for contracting HIV infection. Methamphetamine (METH), a psychostimulant with high abuse potential, may also be toxic to brain DA neurons. Thus, the combination of METH abuse and HIV infection may lead to substantial alterations in DA neuron functioning. The present experiments examined how Tat, alone and with METH, affects DA release in the striatum. Male rats were given an intrastriatal injection of Tat (25 micro g) or vehicle 24 h before treatment with saline or neurotoxic doses of METH. Seven days later microdialysis studies were carried out to measure potassium- and amphetamine-evoked overflow of DA from the striatum. The Tat treatment alone led to no change in potassium-evoked overflow of DA, a 20% decrease in amphetamine-evoked overflow of DA, and a 16% decrease in striatal DA content. The METH alone led to a 37-42% decrease in striatal DA overflow and content. The combined treatment with Tat and METH led to significantly greater 70-78% decreases in striatal DA overflow and content. These results indicate that Tat enhances METH-induced reductions in striatal DA release and content, possibly in a synergistic manner, and suggest that METH abusers infected with HIV may be at increased risk for basal ganglia dysfunction.
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PMID:HIV-1 protein Tat potentiation of methamphetamine-induced decreases in evoked overflow of dopamine in the striatum of the rat. 1293 47

Striatal cholinergic interneurons located in the dorsal striatum and nucleus accumbens are amenable to influences of the dopaminergic mesolimbic pathway, which is a pathway involved in reward and reinforcement and targeted by several drugs of abuse. Dopamine and acetylcholine neurotransmission and their interactions are essential to striatal function, and disruptions to these systems lead to a variety of clinical disorders. Dopamine regulates acetylcholine release through dopamine receptors that are localized directly on striatal cholinergic interneurons. The dopamine D2 receptor, which attenuates acetylcholine release, has been implicated in drug relapse and is targeted by therapeutic drugs that are used to treat a variety of neurological disorders including Tourette Syndrome, Parkinson's disease and schizophrenia. The present study provides the first direct evidence for the localization of dopamine D2 receptors on striatal cholinergic interneurons of the rat brain using dual labeling immunocytochemistry procedures. Using light microscopy, dopamine D2 receptors were localized on the cell somata and dendritic and axonal processes of striatal cholinergic interneurons in the dorsal striatum and nucleus accumbens of the rat brain. These findings provide a foundation for understanding the specific roles that cholinergic neuronal network systems and interacting dopaminergic signaling pathways play in striatal function and in a variety of clinical disorders including drug abuse and addiction.
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PMID:Localization of dopamine D2 receptors on cholinergic interneurons of the dorsal striatum and nucleus accumbens of the rat. 1296 26


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