Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine the effects of low doses of apomorphine on motor performance. Six rats were rewarded with sugar water on a partial reinforcement schedule for pressing force-sensitive beams with a minimum force of 1 g. The kinetics of individual responses and the temporal characteristics of response sequences were measured; open field locomotor activity was also measured in a separate apparatus. Apomorphine (APO), amphetamine (AMP), and haloperidol (HAL) were administered systemically. It was found that low doses of APO (0.03 and 0.1 mg/kg, SC) produced weaker and longer beam presses. These decreases in response peak force resulted from decreases in the rate of rise of force. APO also caused disproportionate lengthening of beam release time. In addition, the low doses of APO increased the time intervals between consecutive components of response sequences. These low doses of APO are known to decrease dopaminergic tone. Hence, the observed pattern of motor dysfunctions produced by APO is similar to the bradykinesia seen in human Parkinson's disease.
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PMID:Low doses of apomorphine suppress operant motor performance in rats. 880 41

The present study examined the effects of bilateral 6-hydroxydopamine lesions in the ventrolateral striatum on the operant behavior of rats. Use of the specially modified operant chambers allowed the measurement of forelimb response force and duration as well as the time intervals between selected behavior in the press-consume-press sequence. More specifically, four time intervals between separate behavioral events were measured: 1) the time from the end of forelimb response to entry of muzzle into the reinforcement well, 2) the time from muzzle entry to the first tongue lick of the water reinforcer; 3) the time from the last lick to muzzle withdrawal from the reinforcement well, and 4) the time from muzzle withdrawal to the beginning of the next forelimb operant response. As determined by neurochemical (HPLC) analysis, the lesioned group exhibited dopamine levels that were 35% of the control group. The operant behavioral deficits were most profoundly appeared in the first week of postoperative test. Behaviorally, the lesioned group exhibited longer forelimb response durations (bradykinesia), and decrements were seen in both the number of muzzle entries and the number of recorded licks during reward consumption. Furthermore, the lesion significantly increased the average latency to switch from the forelimb response to the entry of the muzzle into the reward well. The latency from well entry to the first tongue extension to the reward was also increased by the lesion. These data support the view that the rodent neostriatum is important in the control of behavioral sequences for psychomotor function and at the same time demonstrate the utility of new quantitative behavioral methods for investigating such functions.
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PMID:Quantifying operant behavior deficits in rats with bilateral 6-hydroxydopamine lesions of the ventrolateral striatum. 930 43

Thyrotropin-releasing hormone (TRH) has been reported to have some possibilities toward the treatment of affective CNS disorders. However, long term treatments with daily injections are often required. Effects of TRH-SR (sustained release microspheres of TRH) which is encapsulated in copoly (dl-lactic/glycolic acid) using an in-water drying method were investigated in experimental Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test and high performance liquid chromatography (HPLC) with an electrochemical detector (ECD). We have already reported that in adult Fischer rats killed 12 weeks after infection with JEV at the age of 13 days a marked decrease of tyrosine hydroxylase-positive neurons was found in the bilateral substantia nigra. TRH-SR (3 mg/kg per 2 weeks, 4 times injections, subcutaneous [s.c.]) improved bradykinesia observed in the JEV-induced parkinsonism rats. Dopamine (DA) concentrations in the JEV-infected rats were profoundly reduced in the striatum as compared with controls. TRH-SR (3 mg/kg, once, s.c.) increased DA in the striatum 7 days after the injection. Although the pathomechanism of post-encephalitic parkinsonism is different from that of Parkinson's disease and TRH possesses a variety of CNS effects as well, these results suggest that TRH-SR play a possible role in the treatment of Parkinson's disease in addition to post-encephalitic parkinsonism as a supportive drug of L-DOPA.
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PMID:Sustained release dosage of thyrotropin-releasing hormone improves experimental Japanese encephalitis virus-induced parkinsonism in rats. 974 96

The autopsy findings of an 82-year-old man with history of solitary living in the jungle of Guam, the endemic area of parkinsonism-dementia complex(PDC), for 28 years was reported in this paper. When he was 75 years old, about 20 years later to have come back to Japan, he developed parkinsonism. He noticed bradykinesia and was pointed out masked face, rigidity and tremor in his right hand. After 2 years, he was diagnosed as Parkinson's disease under the third degree of Hoehn-Yahr criteria. He also showed mild cognitive dysfunction, but no pyramidal signs, muscle atrophy of fasciculation at all. Anti-parkinsonian drugs were effective for his motor symptoms. He admitted at age 82 because of anorexia, and died after 3 months. Neuropathological study disclosed neuronal loss and gliosis with Lewy bodies in the substantia nigra, locus coeruleus and dorsal vagal nucleus. There were cortical type Lewy bodies in the limbic system and scanty amount in the neocortex. A few neurofibrillary tangles(NFT) were found in the hippocampus and parahippocampal gyrus, but no dominancy in the second or third layers of the cerebral cortex as reported in PDC. Senile plaques were not observed at all. Although the exact cause of PDC has not been clarified, environmental factors such as water or food seem to influence on the outcome of PDC. However, the pathological findings of the present case were compatible to those of idiopathic Parkinson's disease. Thus it is a very important fact that the present case was not suffered from PDC in spite of his long residence in the endemic area of Guam.
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PMID:[An autopsy of parkinsonism after solitary living in Guam Island for 28 years]. 1072 57

Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy expenditure. Here we report that total energy expenditure (doubly labeled water) measured in 89 nondiabetic Pima Indians was 244 kcal/ day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.056). The 24-h resting energy expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.026). These findings are the first evidence that a genetic mutation is associated with reduced energy expenditure in humans. Because the impact of this mutation on human obesity is small, we suggest that either the energy deficit induced is not large enough to significantly influence body weight in this population and/or that the Cys311-encoding allele is also associated with reduced energy intake.
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PMID:A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure. 1128 60

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was performed in a patient with Huntington's disease (HD) with severe chorea. Stimulation at 40 and 130 Hz improved chorea. Stimulation at 130 Hz slightly worsened bradykinesia overall, whereas 40 Hz had little effect. A [15O] H2O positron emission tomography showed increased regional cerebral blood flow in motor decision making and execution areas more evident at 40 Hz. Adjustment of stimulation parameters in GPi DBS may have the potential to optimize the motor response in HD, improving chorea without aggravating bradykinesia.
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PMID:Bilateral globus pallidus stimulation for Huntington's disease. 1598 18

The aim of this study was to determine whether Acanthopanax senticosus Harms (ASH) offers protection against Parkinson's disease (PD) and its related depressive behaviors in rats administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We examined how ASH affected the MPTP-induced loss of tyrosine hydroxylase (TH)-positive neurons in the midbrain of rats. Extract from the stem bark of ASH prepared with hot water was dissolved in distilled water. Rats were then orally administered ASH (250 mg/kg) once a day for 2 weeks before ASH administration plus an intraperitoneal injection of MPTP (20 mg/kg). The pole test and catalepsy test were used to evaluate the effects of ASH administration on bradykinesia and depressive behaviors in the PD model of rats given MPTP for 2 weeks. Treatment with ASH for 2 weeks resulted in prophylactic effects on MPTP-induced Parkinsonian bradykinesia and catalepsy. Immunohistochemistical analysis using TH antibody showed that ASH provided cytoprotective effects against MPTP-induced loss of dopamine (DA) cells. The present results suggest that it may be possible to use ASH for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to toxic substances.
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PMID:Acanthopanax senticosus Harms as a prophylactic for MPTP-induced Parkinson's disease in rats. 1570 78

Whereas behavioral impairments after stroke are increasingly studied in the rat, little is known about the long-term functional consequences of focal ischemia in the mouse. To address this issue, Swiss mice underwent transient (60 min) intraluminal occlusion of the middle cerebral artery (MCAo) or sham surgery. Sensorimotor (chimney, accelerating rotarod, pole, corner, adhesive removal and staircase tests) and cognitive (passive avoidance and Morris water maze) performances were regularly assessed during 1 month, after which the final histological lesion was measured. Motor coordination and balance, assessed by the chimney and rotarod tests, were transiently altered by MCAo. Moreover, bradykinesia was evidenced by the pole test. The most striking and long-lasting (1 month) sensorimotor deficits were postural asymmetries on the corner test, bilateral skilled forepaw reaching deficits on the staircase test and a contralateral sensorimotor impairment on the adhesive removal test. MCAo animals showed normal spatial learning abilities on the Morris water maze test, but they displayed learning deficits measured by the passive avoidance test. This latter deficit was significantly correlated with both cortical and striatal damage. Our findings demonstrate the usefulness of three tests that had never been reported in the mouse after ischemia: the adhesive removal, staircase and pole tests, which showed deficits 1 month after ischemia and should therefore constitute meaningful tools in mice for assessing both neuroprotective and regenerative therapies in stroke preclinical studies.
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PMID:Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse. 1706 78

Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP.
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PMID:Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury. 2145 62

Deficits in tongue function in conjunction with airway compromise can contribute to dysphagia associated with Parkinson disease (PD). However, it is unknown if these deficits are related to the primary disease pathology in PD, nigrostriatal dopamine depletion. To directly study the impact of striatal dopamine depletion on tongue function, we used unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle and measured tongue force and timing parameters during a complex tongue protrusion task for a water reward. Maximal and average forces were significantly diminished and average press time was significantly longer after neurotoxin administration, reflecting aspects of bradykinesia and hypokinesia associated with PD. Our findings suggest that even unilateral deficits to the nigrostriatal dopamine system may be contributing to some of the lingual sensorimotor deficits seen in PD. Because previous research in rat models of PD has shown that targeted training of the limb can rescue behavioral deficits and spare striatal dopamine neurons, early intervention for cranial sensorimotor deficits may also be indicated.
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PMID:Tongue force and timing deficits in a rat model of Parkinson disease. 2145 16


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