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 long-term effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central monoaminergic neurons in young (2-3 months) and aging (12 months) C57BL/6 mice has been studied using neurochemical and immunocytochemical techniques. MPTP treatment (4 x 20 mg/kg i.p. given 12 h apart) resulted in significant depletion of dopamine (DA) concentration in the striatum, substantia nigra, nucleus accumbens, and olfactory tubercle 1 week after treatment in both young and aging mice. Although a decreased DA concentration in the ventral tegmental area was not seen in young mice, aging mice did show a significant decrease. The extent of decrease of DA concentration was greater in aging mice than in young mice in all areas investigated except in dorsal striatum. The long-term effect of MPTP on DA neurons in young mice included considerable recovery of DA concentration in both nigrostriatal and mesolimbic DA systems following the initial profound depletion; such recovery was minimal in aging mice, even 3 months after MPTP treatment. In young mice treated with MPTP, no significant change of norepinephrine (NE) or serotonin (5-HT) concentration was observed in any area investigated while a significant decrease of NE and 5-HT concentration was seen in several brain areas investigated in aging mice. Immunocytochemical analysis revealed that the MPTP injection resulted in marked disappearance of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in striatum of both young and aging mice 1 week following treatment. Partial recovery of TH-IR fibers was seen 5 weeks or 3 months after MPTP treatment in young mice, while no such apparent recovery was seen in aging mice. Aging mice also showed significant decrease in the number of TH-positive cell bodies in the substantia nigra and ventral tegmental area through all periods investigated, while such a significant decrease was only seen in the substantia nigra of young mice 1 week after treatment. We conclude that aging mice are more sensitive to MPTP and show more widespread damage to the monoaminergic systems than young mice, suggesting that MPTP-treated aging mice provide a more useful model for studying anatomical and neurochemical characteristics of Parkinson's disease than young mice.
 ...
PMID:Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis. 197 65

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate.
 ...
PMID:Odor identification deficit of the parkinsonism-dementia complex of Guam: equivalence to that of Alzheimer's and idiopathic Parkinson's disease. 204 98

The present study comprises a cytoarchitectonic analysis of the human substantia nigra (SN) and ventral tegmental area (VTA); a discussion of their chemoarchitecture and fiber connections (mainly based on tract-tracing studies in primates) preceded by an overview of the wealth of tract-tracing data in rodents; a discussion of the involvement of the SN/VTA complex in Parkinson's disease (PD) and related disorders and in Alzheimer's disease (AD), including some quantitative data; and finally, some functional and pathophysiological considerations, relating nigral organization to pathophysiology and hypotheses on the etiology and distribution of AD and PD. DAergic cell populations in the mesencephalon (SN pars compacta, VTA, and the retrorubral area A8) which give rise to well-developed, DAergic, mesotelencephalic pathways, including a distinct mesostriatal system, and a substance P-immunoreactive striatotegmental system which projects to the SN pars reticulata and VTA appear to be common to reptiles, birds, and mammals (Sect. 3.1). The extensive literature on the organization of the SN/VTA complex in rats is summarized in Sect. 3.2. The mesotelencephalic projection is organized along inverted dorsal to ventral, medial to lateral, and rostral to caudal topographies. A dense DAergic innervation is characteristic of the entire striatal complex, including the caudate-putamen (the dorsal striatum), the nucleus accumbens, and the olfactory tubercle (the ventral striatum). This mesostriatal projection is compartmentally organized with distinct sets of DAergic neurons projecting to striosomes and extrasriosomal matrix, respectively, suggesting specialized channels directed at DAergic modulation of sensorimotor processing in the striatal matrix and limbic related mechanisms represented in the striosomal system. The VTA and medial part of the SN give rise to the DAergic mesolimbocortical system with extensive projections to limbic, allocortical, and neocortical structures. The striatonigral output pattern in rats is organized in such a way that the dorsal striatum mainly innervates the SN pars reticulata, whereas the ventral striatum projects predominantly to the VTA and medial part of the SN. Within the striatonigral projections in rats some interesting channels can be recognized, relating the sensorimotor cortex, via its corticostriatal projections, to that region of the SN giving rise to the nigrothalamic projection, and the visual cortex to the nigrotectal component of the SN pars reticulata.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The human substantia nigra and ventral tegmental area. A neuroanatomical study with notes on aging and aging diseases. 205 66

Superoxide dismutase (SOD) is an important enzyme which is involved in the dismutation of the toxic radical, superoxide anion. The activity of CuZnSOD is increased in patients who suffer from Down's Syndrome, Alzheimer's disease, and in Parkinson's disease. In order to evaluate the contribution of this enzyme to the neuropathology of these neurodegenerative diseases, transgenic mice have been constructed which express the human CuZnSOD gene. As a first step towards exploring these issues, we have carried out an autoradiographic binding study of the distribution of the catecholaminergic uptake blocker mazindol in the brain of these transgenic mice and of their littermates. Desmethylimipramine (DMI)-insensitive [3H]mazindol binding sites which correspond to dopamine uptake sites were located in the striatum, the nucleus accumbens, the olfactory tubercle and in the substantia nigra. Within the striatum, there was a lateromedial gradient, with higher concentration of dopamine uptake sites being found laterally. These findings suggest that subregions of the basal ganglia may be more susceptible to the deleterious effects of dopaminotoxic drugs which are taken up into the dopaminergic neurons via these uptake sites. Saturation experiments revealed no differences in the characteristics of [3H]mazindol binding sites between the two groups of mice. Thus, increased activity of SOD is not associated with diffuse changes in the molecular structures of receptors in mice brain.
 ...
PMID:Quantitative autoradiographic distribution of [3H]mazindol-labeled dopamine uptake sites in the brains of superoxide dismutase transgenic mice. 211 56

The diverse physiological actions of dopamine are mediated by its interaction with two basic types of G protein-coupled receptor, D1 and D2, which stimulate and inhibit, respectively, the enzyme adenylyl cyclase. Alterations in the number or activity of these receptors may be a contributory factor in diseases such as Parkinson's disease and schizophrenia. Here we describe the isolation and characterization of the gene encoding a human D1 dopamine receptor. The coding region of this gene is intronless, unlike the gene encoding the D2 dopamine receptor. The D1 receptor gene encodes a protein of 446 amino acids having a predicted relative molecular mass of 49,300 and a transmembrane topology similar to that of other G protein-coupled receptors. Transient or stable expression of the cloned gene in host cells established specific ligand binding and functional activity characteristic of a D1 dopamine receptor coupled to stimulation of adenylyl cyclase. Northern blot analysis and in situ hybridization revealed that the messenger RNA for this receptor is most abundant in caudate, nucleus accumbens and olfactory tubercle, with little or no mRNA detectable in substantia nigra, liver, kidney, or heart. Several observations from this work in conjunction with results from other studies are consistent with the idea that other D1 dopamine receptor subtypes may exist.
 ...
PMID:Molecular cloning and expression of the gene for a human D1 dopamine receptor. 214 34

The long-term effect of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on pre- and postsynaptic structures of the nigrostriatal and mesolimbic dopamine (DA) system in adult C57BL/6 mice (2 x 40 mg/kg s.c.) was investigated using neurochemical and behavioral methods. It was found that MPTP induced a severe depletion of striatal DA levels (-80%) that persists for 4 weeks after treatment, with less severe effects in nucleus accumbens (-36%) and the olfactory tubercle (-52%). These depletions are associated with decreased tyrosine hydroxylase (TH) activity as determined in vivo and increased turnover of DA. MPTP treatment did not induce any change in the DA2-receptor as determined by [3H]spiperone binding or by two different behavioral tests, i.e. apomorphine-induced climbing and apomorphine-induced stereotypies. No significant weight loss during 4 weeks after MPTP was found. The spontaneous motor activity in these mice was profoundly and persistently depressed (-66%) as a result of the MPTP-induced DA denervation and the motor deficit was completely reversed by L-DOPA treatment. We suggest that MPTP-treated C57BL/6 mice may serve as a suitable model for Parkinson's disease.
 ...
PMID:Chronic neurochemical and behavioral changes in MPTP-lesioned C57BL/6 mice: a model for Parkinson's disease. 227 21

Recent clinical studies have identified significant olfactory deficits in several neuropsychiatric disorders, notably Alzheimer's disease and Parkinson's disease. These have correlated with neurochemical and neuropathological studies of the olfactory system. The presence of a specific sensory deficit may be related to the localisation of pathology within the brain. There is a need for incorporation of olfactory testing into routine clinical examination.
 ...
PMID:Olfaction and psychiatry. 209 62

In the present study we sought to determine whether the olfactory deficits of parkinsonism are related to the cognitive and perceptual-motor manifestations of the disease. Pearson correlation coefficients were computed among a number of olfactory, neurological, and neuropsychological measures obtained from 58 Parkinson's disease patients, including the University of Pennsylvania Smell Identification Test, a modified Randt memory test, a reaction time test, a finger-tapping test, ratings of motor and neurological function, and selected verbal and performance subtests of the Wechsler Adult Intelligence Scale--Revised. Data from 38 patients with Parkinson's disease who received odor detection threshold testing were also evaluated. The intercorrelation matrix was subjected to a principal components factor analysis which yielded six clear-cut factors: cognitive/memory, gross motor, oral motor, fine motor, olfactory, and tremor. The olfactory factor received strong and nearly exclusive loadings from the olfactory measures (which did not evidence meaningful loadings on any of the other factors). A ten-trial jackknife procedure revealed the factor structure to be stable. Further support of the independence of the olfactory variables from the other measures was provided by multiple regression and canonical correlation analyses. Overall, these findings lend support to the hypothesis that the olfactory disorder of parkinsonism is independent of the cognitive, perceptual-motor, and memory manifestations of the disease.
 ...
PMID:The olfactory and cognitive deficits of Parkinson's disease: evidence for independence. 291 66

One of the characteristics of Alzheimer's disease is the early loss of neurons in pathways involved in processing olfactory information. Olfactory function was assessed in subjects with Alzheimer's disease using a conventional Smell Identification Test and a simple three odor match-to-sample problem. The patients exhibited a diminished capacity to identify common odors but were severely impaired in their ability to use novel odors in a match-to-sample task. Subjects with Parkinson's disease had a severe deficit for identifying common odors with the majority scoring as anosmic. Multiple sclerosis was not accompanied by detectable changes in olfactory functioning. The results of the Alzheimer's group are similar to recent animal studies that have shown lesions of the piriform-entorhinal cortex produce a variety of memory deficits that are particularly acute in tasks involving novel odors.
 ...
PMID:Olfactory tests as possible probes for detecting and monitoring Alzheimer's disease. 318 59

To explore the nature of the olfactory dysfunction associated with Parkinson's disease (PD), 81 PD patients who scored well on a cognitive screening test were administered the 40-odorant University of Pennsylvania Smell Identification Test; 38 were additionally given a forced-choice phenylethyl alcohol odor detection threshold test. Clinical ratings of 11 neurologic symptoms (three bilateral) were obtained at the time of testing, and odor identification was retested in 24 patients at intervals ranging from 5 to 39 months. Relative to matched controls, the PD patients exhibited consistent and marked decrements on both types of olfactory tests (ps less than 0.0001). The odor identification deficit was not restricted to any subset of odorants and did not evidence longitudinal change. A factor analysis of the intercorrelations among the variables yielded six easily interpretable factors: general motor, oral motor, olfactory function, cognitive function, tremor, and gender. Olfactory test scores were independent of all other measures, including disease stage and duration. Seventy-two percent of the PD patients were unaware of a smell disorder before testing; those who were aware had significantly lower test scores. A statistical comparison of PD patients' olfactory test scores to those obtained from Alzheimer's disease patients found the olfactory disorders of these diseases to be indistinguishable. The data support the hypothesis that the olfactory deficit of PD is a general and stable one which likely occurs early in the disease process.
 ...
PMID:Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. 339 75


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