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)

Since the initial observation by Brown (1914) that electrical stimulation applied to the habenular efferent bundle in the chimpanzee evoked a pattern of respiration which closely resembled the act of laughter, the habenular complex has remained a mysterious structure. The anatomy of the habenular complex is well delineated (Jones, 1985) forming a major component of the dorsal diencephalic conduction system. Data derived mainly from animal experimentation over the past decade point to the fact that the habenular complex functions as an important link between the limbic forebrain and the midbrain-extrapyramidal motor system. The elucidation of the functions of the habenular complex may thus significantly increase the current insight into the understanding of the interaction between behavioral and motor functions. Clearly, such information would be of great relevance for further understanding of neuropsychiatric disorders such as schizophrenia, Parkinson's disease, Tardive dyskinesia, and Tourette's syndrome in which behavioral and motor impairments are interfaced. This review summarizes anatomical, functional, and pharmacological aspects of the habenular complex and discusses its potential contribution to the pathophysiology of selected neuropsychiatric and movement disorders.
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PMID:Relevance of the habenular complex to neuropsychiatry: a review and hypothesis. 182 82

Little has been written about the cells here termed cerebellar melanoneurons. This paper describes and illustrates their cytologic features and topographic relationships. In the human brain these large pigmented neurons are scattered in a narrow layer near the lateral wall, dorsal angle and roof of the fourth ventricle. They form an inconspicuous part (group A4) of the system of catecholamine, neuromelanin-containing cells well known in the brain stem. Rostrally, a few of them provide a tenuous continuity with the locus ceruleus but topographically the two nuclei are independent. With ordinary stains the cerebellar cells can be seen as early as the 26th week of gestation (the earliest period examined). Brown neuromelanin granules do not appear until two and a half years of age but argentaffin granules, foreshadowing the production of pigment, are found in increasing numbers in the fetal and postnatal period. Homologues of the human cerebellar cells are reported in two species of monkey, Macaca nemestrina and Lagothrix sp. Neuromelanin, not previously observed in non-human cerebellar cells, occurs in M. mulatta and M. nemestrina. The proximity of the cerebellar melanoneurons to the ventricle raises the possibility that they are related to functions of the ependyma, or that they influence, or are affected by, constituents of the cerebrospinal fluid. The pathologic changes they undergo in Parkinson's disease and other disorders are to be described elsewhere.
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PMID:The melanoneurons of the human cerebellum (nucleus pigmentosus cerebellaris) and homologues in the monkey. 395 55

A modified version of the odd-man-out test was used to investigate set-shifting aptitude in 12 patients with Parkinson's disease. We asked subjects to execute in alternation two different sorting rules over successive items. External and internal cueing conditions were employed. Patients with Parkinson's disease were impaired on the tasks with internal cues but were normal on the tasks with external cues. Moreover, the shift costs were consistently larger for the shift to the easier task than the shift to the more difficult task. These findings indicated that the model of 'Supervisory Attentional System' may not be sufficient to explain the data as Brown and Marsden (1988) originally suggested.
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PMID:Set-shifting aptitude in Parkinson's disease: external versus internal cues. 750 74

Severe mitochondrial genetic mutations lead to early degeneration of specific human tissues; milder mitochondrial mutations may cause degeneration at a later point in life. A mutation at position 4336 was reported to occur at increased frequency in individuals with Alzheimer disease (AD) and Parkinson disease [Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. F., Mirra, S. S., Beal, M. F., Yang, C.-C., Gearing, M., Salvo, R., Watts, R. L., Juncos, J. L., Hansen, L. A., Crain, B. J., Fayad, M., Reckord, C. L. & Wallace, D. C. (1993) Genomics 17, 171-184]. We have investigated the notion that this mutation leads to excess risk of AD by using a case-control study design of 72 AD autopsies and 296 race- and age-matched controls. The 4336G mutation occurred at higher frequency in AD autopsies than age-matched controls, a statistically significant difference. Evolutionary analysis of mtDNAs bearing the 4336G mutation indicated they were more closely related to each other than to other mtDNAs, consistent with the model of a single origin for this mutation. The tight evolutionary relatedness and homoplasmy of mtDNAs that confer elevated risk for a late-onset disease contrast strikingly with the distant relatedness and heteroplasmy of mitochondrial genomes that cause early-onset disease. The dichotomy can be explained by a lack of selection against mutations that confer a phenotype at advanced age during most of the evolution of humans. We estimate that approximately 1.5 million Caucasians in the United States bear the 4336G mutation and are at significantly increased risk of developing mitochondrial AD in their lifetime. A mechanism for 4336G-mediated cell death is proposed.
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PMID:A mitochondrial DNA clone is associated with increased risk for Alzheimer disease. 762 38

Rats have been described as being insensitive to relatively high doses of systemically administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that in primates induces a neurological syndrome identical to idiopathic Parkinson's disease. The current explanation for the rat resistance is that most of the MPTP is converted into the toxic metabolite 1-methyl-4-phenylpyridium (MPP+) by the MAO-B present in the brain vessel endothelium. Since MPP+ is a polar compound, a very low amount could cross the blood-brain barrier and be present inside the brain. We administered C57 BL mice and Brown Norway rats with either MPTP (30 mg/kg, ip) or the combined treatment MPTP + diethyldithiocarbamate (DDC). In mice, DDC prolonged the striatal exposure to MPP+, potentiated the MPTP-induced acute syndrome, and enhanced the MPTP-induced striatal dopamine depletion. In rats, DDC potentiated the MPTP-induced acute syndrome, but no changes in the striatal dopamine were observed after either MPTP or DDC + MPTP administration. Also in rats, however, high doses of MPP+ were measured in the striatum of MPTP-alone treated rats and DDC delayed the MPP+ elimination from the striatum. When MPTP alone or DDC + MPTP was administered to rats unilaterally lesioned with 6-hydroxy dopamine (6-OH-DA), the levels of MPP+ measured in the intact striatum were significantly higher than those found in the 6-OH-DA-lesioned striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In brown Norway rats, MPP+ is accumulated in the nigrostriatal dopaminergic terminals but it is not neurotoxic: a model of natural resistance to MPTP toxicity. 820 Apr 37

Short-term memory deficits are prominent in untreated Parkinson's Disease (PD) and speed of central processing is known to be abnormal. To investigate the relationship between these findings, a modification of the Brown-Peterson paradigm was given to newly diagnosed, untreated patients and healthy control subjects (HCS). The PD patients were impaired under conditions of long stimulus exposure but not when study time was short. Although patients displayed deficits in immediate recall, they were more impaired at longer test delays. They achieved fewer encoding operations per unit time, resulting in a divergence of group performance with increasing duration of stimulus exposure. Performance in the PD group did not associate with motor disability, disease duration or rating of depression. These results are discussed in terms of a unifying reduced central processing deficit that is evident in PD but is independent of physical symptoms.
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PMID:Encoding deficits in untreated Parkinson's disease. 834 23

In his extensive writings, Denny-Brown hypothesized that two competitive 'tropisms,' one positive (exploratory) and one negative (withdrawal) act to coordinate normal movements at all levels of the neuraxis. Lesions in particular areas of the central nervous system result in disequilibrium between these tropisms, leading to disorders of posture and movement, including involuntary movements. The tactile manifestations of unbalanced exploratory tropisms are grasping responses, whereas the complementary withdrawal tropisms are avoiding responses. In Denny-Brown's view, at the level of the cerebral cortex, grasping responses result from frontal lobe injury whereas avoiding responses result from parietal lobe lesions. In this report we review Denny-Brown's conceptions of positive and negative tropisms, their anatomical loci, and whether his hypothesis has merit in a contemporary approach to brain function. We find that Denny-Brown's view on the anatomical loci associated with these behaviors is incomplete, but that the idea of conflicting behavioral tendencies is valuable for understanding and managing some neurological and perhaps also psychiatric disorders. For example, his hypothesis offers an important perspective in understanding the paradoxical success of stereotaxic surgery to alleviate the symptoms of Parkinson's disease.
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PMID:Positive and negative factors in movement control: a current review of Denny-Brown's hypothesis. 934 69

Previous studies have implicated mitochondria-derived reactive oxygen species (ROS) in both the aging process and age-related diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease etc. The current study, utilizing electron paramagnetic resonance (EPR) spectrometry, was designed to determine if mitochondrial respiratory stimulation, under state 4 conditions, caused extensive oxidative modifications to membrane cytoskeletal proteins and lipids in the brain. A mixed population of cortical synaptosomes and mitochondria, prepared by centrifugation techniques using rat brain cortex from adult (4-6 months) female Brown Norway rat brains, were labeled with the lipid-specific spin probe, 5-nitroxyl stearate (5-NS). Stimulation of the mitochondrial electron transport chain was accomplished using 20 mM succinate at 25 degrees C for 3 h. Mitochondrially derived free radicals, when reacted with the paramagnetic center of the spin probe, result in a loss of paramagnetism resulting in loss of intensity. A significant lowering (23%, P<0.0001) in the signal amplitude (B0) of 5-NS, indicative of generation of oxyradicals, was found. The order parameter, an inverse EPR-measure of membrane fluidity of the 5-NS spin labeled mitochondrial and synaptosomal membranes, also decreased following mitochondrial respiratory stimulation (P<0.005). Changes in the physical state of cytoskeletal and transmembrane proteins due to succinate oxidation were measured using MAL-6 (2,2,6, 6,-tetramethyl-4 maleimidopiperdin-1-oxyl), a thiol-specific nitroxide spin label. The ratio of the amplitudes of the weakly to strongly immobilized spin label reaction sites (W/S ratio) in the low-field region of the spectrum was used to determine any alteration in protein conformation. Previous studies in our laboratory have established that increased protein oxidation is associated with a decreased W/S ratio. In the current study, our results indicated significant lowering of the W/S ratio in cortex (30%, P<0.0001) upon stimulation of the mitochondria with 20 mM succinate. Thus, we conclude that respiratory stimulation of mitochondria, due to a hypermetabolic stress with succinate, caused significant oxidative modifications of cortical membrane lipids and proteins.
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PMID:Effects of mitochondrial respiratory stimulation on membrane lipids and proteins: an electron paramagnetic resonance investigation. 967 68

Indirect evidence from human and monkey investigations supports the idea that impaired frontal tasks in Parkinson's disease (PD) may result from striato-frontal disruption caused by dopamine (DA) denervation of the caudate nucleus. To directly investigate this hypothesis, we used PET with 11C-S-Nomifensine (11C-S-NMF), a sensitive marker of striatal DA denervation, in 10 non-demented PD patients in whom two frontal executive tests, the object alternation (OA) and the conditional associative learning (CAL) tasks, thought to reflect mainly set-shifting/inhibition and planning, respectively, were given. In addition, the central executive function of verbal working memory was assessed with the Brown Peterson paradigm (BPP). We found a highly significant correlation between right caudate 11C-S-NMF specific binding and OA performance, less significant and reverse-direction correlations between CAL performance and putamen 11C-S-NMF binding, and no significant correlation with BPP performance. Thus, caudate DA denervation may subtend poor set-shifting/inhibition process in PD. Our results also point to distinct and complex relationships between striatal DA and specific frontal tasks.
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PMID:Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease. 1002 3

The aim of the present work was to evaluate verbal working memory in patients affected by Parkinson's disease (PD). In particular, tests that explore the functionality of the Articulatory Loop and of the Central Executive during verbal tasks were given. PD patients displayed normal phonological similarity, word length and word frequency effects in a Word span task, thus demonstrating adequate retention capacity of the phonological store, normal functioning of the articulatory rehearsal mechanism and a normal contribution of lexical-semantic knowledge to verbal immediate recall. In the Brown-Peterson task, PD patients showed abnormal performance decay on the letter recall task when articulatory rehearsal was inhibited by a serial subtraction concurrent task. These data provide evidence for normal functioning of the Articulatory Loop in PD patients. However, when the verbal recall task is more attention demanding, PD patients show deficient performance levels, presumably due to depleted processing resources by the Central Executive.
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PMID:Verbal working memory deficit in Parkinson's disease subjects. 1047 80


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