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 positive-negative distinction of schizophrenia has emerged as a valid means of clarifying its heterogeneity. Despite evidence that the two symptom classes may reflect different dimensions of the disease, there is presently no integrated model for understanding of the pathophysiology of these symptoms and their co-occurrence in schizophrenia. We propose that negative phenomena of schizophrenia may be a variant of Parkinsonism. This view is supported by the overlap with Parkinsonism in terms of clinical features, neurochemistry, pharmacology, as well as neuroradiological and neuropathological aspects. As such, negative symptoms may be a manifestation of disease of the basal ganglia and constitute the core pathology in schizophrenia. Positive symptoms, conversely, may reflect an "accessory" process related to a compensatory increase in striatal and limbic dopamine activity following an injury to the dopaminergic system. In the present communication we present a series of studies that support the association of negative schizophrenia and Parkinsonism. Based on this evidence, we suggest that schizophrenic patients with prominent negative symptoms might be managed like patients with Parkinson's disease, namely, with dopaminergic drugs and MAO-B inhibitors. Finally, the association of negative schizophrenia with Parkinsonism raises the possibility that adrenal medullary tissue transplantation, which may benefit a selected group of Parkinsonian patients, may be a future promising therapy for refractory negative schizophrenia.
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PMID:The relationship of negative schizophrenia to parkinsonism. 214 20

In the present paper it is shown that when either of the noncompetitive NMDA antagonists MK-801 or ketamine are combined with the alpha-adrenergic agonist clonidine, a pronounced stimulation of locomotion is produced in monoamine-depleted mice. Likewise, when a subthreshold dose of MK-801 is combined with the muscarinic antagonist atropine, a forceful synergism with regard to locomotor activity in monoamine-depleted mice is observed. Furthermore, the present study shows that also in monoamine-depleted rats MK-801, as well as the competitive NMDA antagonist AP-5 (DL-2-amino-5-phosphonovaleric acid), interact synergistically with clonidine to enhance locomotor activity. Taken together, our findings suggest that central glutamatergic systems exert a powerful inhibitory influence on locomotion. Interfering with this inhibitory force by administration of an NMDA antagonist promotes locomotion and discloses the activational potential of other transmitter systems. The results are discussed in relation to 1) the pathophysiology of schizophrenia, with emphasis on the glutamate hypothesis of schizophrenia, and 2) implications for the treatment of Parkinson's disease.
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PMID:Interfering with glutamatergic neurotransmission by means of NMDA antagonist administration discloses the locomotor stimulatory potential of other transmitter systems. 216 45

The importance of the dopaminergic system in brain function has been emphasized by its association with neurological and psychiatric disorders such as Parkinson's disease and schizophrenia. On the basis of their biochemical and pharmacological characteristics, dopamine receptors are classified into D1 and D2 subtypes. As the most abundant dopamine receptor in the central nervous system, D1 receptors seem to mediate some behavioural responses, modulate activity of D2 dopamine receptors, and regulate neuron growth and differentiation. The D dopamine receptor has been cloned by low-stringency screening. We report here the cloning of human and rat D1 dopamine receptors by applying an approach based on the polymerase chain reaction. The cloned human D1 dopamine receptor has been characterized on the basis of four criteria: the deduced amino-acid sequence, which reveals that it is a G protein-coupled receptor; the tissue distribution of its messenger RNA, which is compatible with that of the D1 dopamine receptor; its pharmacological profile when transfected into COS-7 cells; and its ability to stimulate the accumulation of cyclic AMP in human 293 cells.
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PMID:Cloning and expression of human and rat D1 dopamine receptors. 216 20

The loss of midbrain dopamine in Parkinson's disease is accompanied by a matching loss in the dopamine transporter and a rise in the D1 and D2 receptor densities. This is found in the brain putamen and caudate tissues from unmedicated patients, and may account for the good early clinical response to L-dopa. Long-term L-dopa treatment reverts the receptor densities toward normal levels. Positron emission tomography (PET) data and in vitro data generally concur. In schizophrenia the density of the dopamine transporter as well as that of the D1 dopamine receptor is normal. The D2 receptor density, however, is consistently elevated in postmortem brain putamen and caudate nucleus, even in tissues from neuroleptic-free or drug-naive patients. Three sets of PET and single photon emission computed tomography (SPECT) data support the postmortem findings. Early evidence indicating abnormal D2 structure as well as a reduced link between D1 and D2 warrant a detailed study of the genes for these two receptors in schizophrenia.
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PMID:Dopamine receptors and transporters in Parkinson's disease and schizophrenia. 219 54

Alterations in blink rate have been reported in several neuropsychiatric disorders presumed to result from abnormal central dopaminergic functions. Increased blink rate in schizophrenia, Tardive dyskinesia, Tourette's syndrome and Meige's disease are associated with enhanced dopaminergic functions. Parkinson's disease is associated with reduced dopaminergic functions and decreased blink rate. Thus, blink rate may reflect striatal and mesolimbic dopaminergic activity. Since acute light exposure suppresses melatonin production and darkness stimulates melatonin secretion, blinking may serve to regulate light-dark exposure to the pineal gland and thus to 'fine tune' melatonin production. As there is evidence to suggest that melatonin inhibits the release of dopamine in the striatum and limbic system, increased blink rate may serve to reduce light exposure, increase melatonin secretion and attenuate dopaminergic functions. Conversely, decreased blinking (as is observed in patients with Parkinson's disease) could reflect a compensatory mechanism to increase light exposure, reduce melatonin production and ultimately increase dopamine functions. This model is novel in that for the first time it suggests a functional link among blink rate, melatonin secretion and striatal dopaminergic functions in movement disorders.
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PMID:The significance of eye blink rate in parkinsonism: a hypothesis. 226 15

Spontaneous blink rates are controlled by a definable neural system originating in PPRF with facilitatory modulation from SN and superior colliculus and inhibitory modulation provided by cerebellum and occipital cortex. The thalamus may also be involved but the result of its influence is not clear. Reflex blinking is often reduced when spontaneous blink rate is increased and the reverse applies as well. The anatomic control of reflex is primarily in structures in the caudal half of pontine tegmentum and rostral midbrain. However, SN and cerebellum and other structures that regulate blink rate also modulate reflex blinking. Neurochemical control as determined by neuropharmacological experiments is exerted by dopaminergic, cholinergic and GABAergic systems of brain stem. Dopamine activity correlates directly with blink rate whereas agonism of the other two relevant neurotransmitter systems may inhibit blink rate. Clinical implications in central nervous system disease are currently restricted to Parkinson's disease, schizophrenia and autism. In the former illness, reduced blink rate signifies a worsening of the illness and a significant increase in blink rate in patients treated with dopamine agonist may be a harbinger of agonist-induced dyskinesia. In schizophrenia, increased blink rate, even in medication-naive subjects, may signify involvement of the structures that regulate blinking. This is important because these structures are rarely invoked as sites of potential pathophysiological import in schizophrenia. Similar considerations apply to autism except that increased blinking more clearly differentiates this disorder from other forms of retardation.
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PMID:Blinking. 248 18

The present study corroborates previous findings showing that the selective, non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)-cyclohepten-5,10-imi ne] produces a dose-dependent increase in locomotion in mice pretreated with a combination of the monoamine-depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine. Moreover, the present investigation demonstrates a synergistic interaction between MK-801 and the alpha-adrenergic agonist clonidine in monoamine-depleted mice: MK-801 in a dose of 1 mg/kg and clonidine in a dose of 2 mg/kg hardly affected locomotion when given separately, but when the two drugs were combined a dramatic enhancement of motor activity was observed. This effect was effectively antagonized by the alpha 2-adrenergic blockers idazoxan and yohimbine, as well as by the "atypical" neuroleptic clozapine. Likewise, a clear-cut synergism was observed when a low dose of the dopamine receptor agonist apomorphine (0.1 mg/kg), which did not per se affect motor activity, was combined with MK-801 (1.5 mg/kg); however, the synergism between apomorphine and MK-801 was less dramatic than that observed between MK-801 and clonidine. The results may have important neuropsychiatric implications related to, e.g. the treatment of Parkinson's disease and the pathogenesis of schizophrenia.
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PMID:Dramatic synergism between MK-801 and clonidine with respect to locomotor stimulatory effect in monoamine-depleted mice. 254 13

The objective of this study is to investigate the type, importance, and incidence of hereditary diseases in patients at the National Institute of Neurology and Neurosurgery in Mexico City. A review of 6,258 files indicated that hereditary diseases represent an important problem for the Institute. Of the diseases with the highest incidences, hereditary factors have an important role in seven (epilepsy, depression, facial palsy, schizophrenia, mental retardation, migraine, and Parkinson's disease). Diseases of known monogenic etiology represent 1.5% of all the cases.
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PMID:Importance of hereditary disease at a Neuropsychiatric Institute in Mexico City. 259 29

Since 1982, grafting of human nervous tissue on human central nervous system has been realized, mainly in Parkinson's disease. The present article reviews the theoretical basis of such procedures, i.e., the remarkable experimental work that began around the turn of the century. New approaches, e.g., using hydroxydopamine or MTPP, have greatly enlarged the field of experimental research. In man, grafts of adrenal medulla and, in a few cases, of fetal substantia nigra, have been realized in several hundreds of patients. The known results invite great caution. Brain grafting has also been considered in Huntington's chorea, trauma of the spinal cord and even schizophrenia. In animals, transplants of hypothalamus and pre-optic area have counteracted genetic endocrine disorders. Experimental researches are of high interest but their application to man raises major problems of efficiency and fundamental ethical and legal questions.
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PMID:[Homografts in the human brain. Current data]. 267 72

The development of psychiatric thought has always been in close association with the pineal gland. The importance of a relationship between pineal, and mental functions was stressed by Descartes when he placed the seat of rational thought as well as the confluence of body and soul in this organ (Cf. Descartes, L'Homme, 1664). His writings exerted such a strong influence that, quite soon indeed, physicians started regarding this gland as being the source of many mental disorders. In an attempt to find and explain a possible link between mental abnormalities, and the discovery of calcified pineals in necroptic studies, many theories were put forward during the 18th, and the 19th century. Afterwards, the importance of the gland went almost unnoticed until 1920, when Becker treated psychotic patients with pineal extracts. An up-to-1950 review by Kitay and Altschule (1954) reported 17 cases where pineal extracts were successfully injected to psychotic patients. In the present review, the author tries and summarizes several reports dealing with the influence of the pineal function on affective disorders, schizophrenia, sleep cycle, Parkinson disease, etc., as a contribution to future research work in this field.
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PMID:[Neuroendocrine and psychopharmacologic aspects of the pineal function. Melatonin and psychiatric disorders]. 269 86


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