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991.
Comparison of clinical types of Wilson's disease and glucose metabolism in extrapyramidal motor brain regions 总被引:3,自引:0,他引:3
Hermann W Barthel H Hesse S Grahmann F Kühn HJ Wagner A Villmann T 《Journal of neurology》2002,249(7):896-901
In Wilson's disease a disturbed glucose metabolism especially in striatal and cerebellar areas has been reported. This is
correlated with the severity of extrapyramidal motor symptoms (EPS). These findings are only based on a small number of patients.
Up to now it is unknown whether EPS are caused by various patterns of disturbed basal ganglia glucose metabolism. We investigated
37 patients and 9 normal volunteers to characterize the disturbed glucose metabolism in Wilson's disease more precisely. The
glucose metabolism was determined in 5 cerebellar and cerebral areas (putamen, caput nuclei caudati, cerebellum, midbrain
and thalamic area) by using
18
F-Fluorodesoxyglucose-Positron-Emission-Tomography ( [
18
F]FDG-PET). The database was evaluated by a cluster analysis. Additionally, the severity extrapyramidal motor symptoms were
judged by a clinical score system. Three characteristic patterns of glucose metabolism in basal ganglia were obtained. Two
of them may be assigned to patients with neurological symptoms whereas the third cluster corresponds to most patients without
EPS or normal volunteers. The clusters can be identified by characteristic consumption rates in this 5 brain areas. The severity
of EPS can not clearly be assigned to one of the clusters with disturbed glucose metabolism. However, the most severe cases
are characterized by the lowest consumption in the striatal area. When there is marked improvement of EPS impaired glucose
consumption reveals a persistent brain lesion. Finally, the neurological symptoms in Wilson's disease are caused by (at least)
two different patterns of disturbed glucose metabolism in basal ganglia and cerebellum. The severity of EPS seems to be determined
by a disturbed consumption in the striatal area.
Received: 6 July 2001, Received in revised form: 14 November 2001, Accepted: 3 December 2001 相似文献
992.
Fedrowitz M Hamann M Rehders JH Richter A Gernert M 《Journal of neuroscience research》2002,68(5):595-603
The dt(sz) hamster is a well-established animal model of idiopathic paroxysmal dystonia. Previous investigations of this mutant have indicated dysfunctions of the gamma-aminobutyric acid (GABA)-ergic system within the basal ganglia. Systemic administration of the central stimulant pentylenetetrazole (PTZ) aggravated dystonia at subconvulsant doses, whereas GABA-mimetic drugs have beneficial effects in dt(sz) hamsters. GABA mimetics also provide clinical benefit in humans with idiopathic paroxysmal dystonia. The spontaneous discharge rates of substantia nigra pars reticulata (SNr) neurons was unaltered in anesthetized dt(sz) hamsters, but systemic application of subconvulsant doses of PTZ caused significantly greater increases of discharge rates in dystonic hamsters compared with nondystonic controls. The present study tested the hypothesis that SNr neurons are more sensitive to local application of PTZ in dt(sz) hamsters than in nondystonic hamsters. PTZ applied locally by pressure injection at 2, 3, and 5 mM to the SNr during in vivo single unit recordings revealed a dose-dependent increase of SNr discharge rates in mutants and controls relative to predrug rates, with a significantly greater increase in mutants at 3 mM PTZ. To examine the functional relevance of the increased susceptibility of SNr neurons to PTZ in mutants, the effects of PTZ on severity of dystonia were investigated after microinjections into the SNr of freely moving dt(sz) hamsters. Bilateral nigral microinjection of 40 ng PTZ did not aggravate dystonia but exerted moderate antidystonic effects. Therefore, the previous findings of prodystonic effects of systemic administration of PTZ in dt(sz) hamsters are related to extranigral effects rather than to the elevation of nigral discharge rates in response to systemic, or locally applied, PTZ. The greater susceptibility of neurons within the SNr to PTZ suggests dysfunctions of the GABA(A) receptor in dt(sz) mutants. 相似文献
993.
This study investigated the feasibility of using a peripheral nerve autograft (NAG) to promote and guide regeneration of sensory axons from the caudal lumbar dorsal roots to the rostral dorsal column following a lower thoracic cordotomy in adult rats. After a left hemicordotomy at the T13 vertebra level and ipsilateral L3 and L4 rhizotomies, a peripheral NAG (peroneal nerve) was connected to the distal roots stumps, then implanted into the left dorsal column 10 mm rostral to hemicordotomy site (n = 12). After surgery, all animals of the experimental group experienced complete anesthesia in their left hindlimb. Three months later, a slight response to nociceptive stimulation reappeared in L3 and/or L4 dermatomes in 6 of the 12 experimental animals. None of these animals exhibited self-mutilation. Nine months after surgery, we performed retrograde tracing studies by injecting horseradish peroxidase (HRP) into the left dorsal column 30 mm rostral to the NAG implantation site. In eight animals, we found HRP-stained neurons in the left L3 and/or L4 dorsal root ganglia (DRG). The mean number of HRP-stained neurons per DRG was 71 +/- 92 (range 2-259). In control groups, no HRP-stained neurons were found in L3 or L4 DRG. Histological analysis of the NAG showed evidence of axonal regeneration in all 8 animals with positive retrograde labeling of DRG neurons. However, we did not find a statistical correlation between the number of HRP-stained neurons and the degree of sensory recovery. This study demonstrates that an NAG joining dorsal roots to the dorsal column, thus shunting the original CNS-PNS junction, can support regeneration of central axons from DRG primary sensory neurons into the dorsal column over distances of at least 30 mm despite the inhibitory influence of the CNS white matter. 相似文献
994.
Sex hormones may exert neuroprotective effects in various models of brain lesions. Male and female Long-Evans rats were subjected to intracerebroventricular injections of 2 microg 192 IgG-saporin or vehicle. Starting 2 days before surgery, half the male rats were treated with estradiol for 7 days. Three weeks after surgery, they were sacrificed for histochemical staining of acetylcholinesterase (AChE) and densitometric evaluations. The lesion induced a substantial to dramatic decrease of the AChE-positive fiber density in the cingulate, somatosensory, piriform, retrosplenial and perirhinal cortices, and in the hippocampus. Weak effects were found in the striatum. There was no significant decrease in the dorsal thalamus. Sex had no significant effect on AChE-positive staining in any brain area. In males, estradiol treatment did not alter the effects of 192 IgG-saporin. These results show that sex or estradiol treatment in male rats does not interfere with the immunotoxic effects of intracerebroventricular injections of 192 IgG-saporin on cholinergic projections from the basal forebrain. 相似文献
995.
Magnetic response imaging has demonstrated increased signal intensities within the basal ganglia in patients with hepatic
encephalopathy; the densities are considered to represent manganese deposition. We measured whole blood manganese concentrations
in nine children with congenital portosystemic venous shunts detected by screening tests for galactosaemia. Beyond 1 year
of age, these patients showed significantly higher manganese concentrations than controls (2.40 ± 0.43 versus 1.48 ± 0.38 μg/dl;
P=0.0001). Four of the nine patients were studied by magnetic response imaging. T1-weighted images showed increased signal
intensities in the basal ganglia of those four patients, suggesting manganese accumulation.
Conclusion Children with congenital portosystemic venous shunts showed manganese elevations in blood and magnetic response imaging changes
in the basal ganglia. These children should avoid excessive manganese intake.
Received: 11 September 2000 / Accepted: 30 November 2000 相似文献
996.
Apicella P 《The European journal of neuroscience》2002,16(11):2017-2026
Analysis of recordings of single neuronal activity in the striatum of monkeys engaged in behavioural tasks has shown that tonically active neurons (TANs) can be distinguished by their distinct spontaneous firing and functional properties. As TANs are assumed to be cholinergic interneurons, the study of their physiological characteristics allows us to gain an insight into the role of a particular type of local-circuit neuron in the processing of information at the striatal level. In monkeys performing various behavioural tasks, the change in the activity of TANs, unlike the diversity of task-related activations exhibited by the phasically active population of striatal neurons, involves a transient depression of the tonic firing related to environmental events of motivational significance. Such events include primary rewards and stimuli that have acquired a reward value during associative learning. These neurons also respond to an aversive air puff, indicating that their responsiveness is not restricted to appetitive conditions. Another striking feature of the TANs is that their responses can be modulated by predictions about stimulus timing. Temporal variations in event occurrence have been found to favour the responses of TANs, whereas the responses are diminished or abolished in the presence of external cues that predict the time at which events will occur. These data suggest that the TANs respond as do detectors of motivationally relevant events, but they also demonstrate that these neurons are influenced by predictive information based on past experience with a given temporal context. TANs represent a unique subset of striatal neurons that might serve a modulatory function, monitoring for temporal relationships between environmental events. 相似文献
997.
Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum 总被引:7,自引:0,他引:7
Napolitano M Centonze D Calce A Picconi B Spiezia S Gulino A Bernardi G Calabresi P 《Neurobiology of disease》2002,10(3):387-395
The irreversible loss of the dopamine-mediated control of striatal function is considered the functional substrate of the motor symptoms of Parkinson's disease. This pathological event causes a complex rearrangement of neuronal activity which involves specific dopamine-regulated cellular functions and, secondarily, several other cellular properties and transmitter systems. In the present study, we applied recently developed cDNA microarray technology to investigate the genetic correlates of the alterations produced by 6-hydroxydopamine-induced dopamine denervation in the nucleus striatum. We found that chronic dopamine denervation caused the modulation of 50 different genes involved in several cellular functions. In particular, products of the genes modulated by this experimental manipulation are involved both in the intracellular transduction of dopamine signal and in the regulation of glutamate transmission in striatal neurons, providing some information on the possible neuronal events which lead to the reorganization of glutamate transmission in the striatum of parkinsonian rats. 相似文献
998.
999.
Excitatory glutamatergic inputs to the subthalamic nucleus (STN), and subthalamic afferents to the substantia nigra pars reticulata (SNr) are believed to play a key role in the pathophysiology of Parkinson's disease (PD). Previously, we have shown that activation of the group I mGlus in the STN and SNr induces a direct depolarization of the neurons in these nuclei. Surprisingly, although both group I mGlus were present in the STN and SNr, mGlu5 alone mediated the DHPG-induced depolarization of the STN, and mGlu1 alone mediated the DHPG-induced depolarization of the SNr. We now report that both mGlu1 and mGlu5 are coexpressed in the same cells in both of these brain regions, and that both receptors play a role in mediating the DHPG-induced increase in intracellular calcium. Furthermore, we demonstrate that the induction of an acute PD-like state using a 16 h haloperidol treatment produces an alteration in the coupling of the group I receptors, such that post-haloperidol, DHPG-induced depolarizations are mediated by both mGlu1 and mGlu5 in the STN and SNr. Therefore, the pharmacology of the group I mGlu-mediated depolarization depends on the state of the system, and alterations in receptor coupling may be evident in pathological states such as PD. 相似文献
1000.
RATIONALE: Several studies have shown that dopamine D1 agonists act on forebrain dopamine terminal regions to exert many of their behavioral effects. Yet, there is also a large number of D1 receptors in the substantia nigra pars reticulata (SNr), and these receptors are located mainly on terminals of gamma-aminobutyric acid (GABA)-ergic striatonigral neurons. OBJECTIVE: The present studies were undertaken to determine the behavioral and neurochemical effects of local administration of the D1 agonist SKF 82958 and to study the interactions between D1 and GABA mechanisms in SNr. METHODS: Microdialysis methods were used to characterize the effect of SKF 82958 on extracellular GABA, and several experiments studied the effects of nigral D1 stimulation on motor activity and investigated the behavioral significance of D1/GABA interactions in SNr. RESULTS: Local infusion of 10(-6) M SKF 82958 increased extracellular levels of SNr GABA, and this effect was blocked by co-infusion of the D1 antagonist SCH 23390. Bilateral SNr injections of SKF 82958 increased locomotor activity, and this effect was blocked by the GABA-A antagonist bicuculline. Intranigral bicuculline reduced motor activity, while the GABA-A agonist muscimol increased various motor activities in a manner similar to SKF 82958. CONCLUSIONS: The present results suggest that the D1 agonist SKF 82958 acts on D1 receptors in SNr to increase extracellular levels of GABA, and the increase in motor activity produced by nigral D1 stimulation is dependent on stimulation of GABA-A receptors. D1/GABA interactions in SNr are important for the modulation of basal ganglia output, which may have important implications for Parkinson's disease. 相似文献