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1.
Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dtsz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder. 相似文献
2.
P. L. Mensah 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1980,38(3):267-271
Summary The position of the largest striatal neuron within territories delimited by medium-sized clustered neurons was charted in Nissl-stained sections through the mouse caudate-putamen nucleus. Medium-sized neuron somata occur in close proximity to this large cell at some point in the anteroposterior, mediolateral or dorsoventral extent of its soma. The size of the network of medium-sized neurons associated with the large cell may vary from two to 15 neurons. Even when this network is extensive, the large neuron is never completely surrounded. Most often, this cell also borders a fascicle of internal capsule fibers, and the entire cellular island may be aligned either parallel to or perpendicular to the orientation of these fibers. These findings suggest the hypothesis that cellular territories in the caudate-putamen nucleus have a very specific orientation in three dimensional space. 相似文献
3.
A. Moser S. Drescher 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1994,79(2):383-387
Summary Vasoactive intestinal polypeptide (VIP) was incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen (CP) tissue of the rat in order to examine the effect of the peptide on forskolin-activated adenylate cyclase in vitro. Forskolin induced an enhancement of cyclic AMP formation that was mediated by an effect on catalytic subunit and stimulatory guanine nucleotide regulatory protein (Ns). In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by dopamine and sodium fluoride but, in the absence of guanylylimidodiphosphate (guanosine 5-(,y-imido)-triphosphate) VIP inhibited the forskolin-stimulation of the enzyme in a noncompetitive manner. Met-encephalin, acting on a D-2 receptor-coupled putative inhibitory guanine nucleotide regulatory protein (Ni), inhibited the adenylate cyclase activity stimulated by forskolin to a slightly greater extent than VIP. When assayed together, these inhibition effects were additive, implying that the peptide receptors are not identical. The Ni — antagonist, MnCl2 completely blocked the inhibition of met-encephalin but had no significant effect on VIP-induced inhibition. In addition, pertussis toxin did not influence the effect of VIP on forskolin-stimulation in contrast to cholera toxin which did antagonize the VIP effect via the stimulatory guanine nucleotide regulatory protein (Ns). Furthermore, specific D-1 and D-2 dopaminergic receptor antagonists (+)-flupentixol and spiperone had no effect on VIP-modulated forskolin-stimulated adenylate cyclase activity. These results suggest that the neuromodulatory effect of VIP is mediated by a Ns distinct from those involved in several adenylate cyclase pools sensitive to stimulation by dopamine and VIP in the rat striatum. 相似文献
4.
Electrical stimulation of the anteromedial cortex (AMC) or striatum of rats evoked contraversive eye, head and body movements. In these experiments we test which neurons and which pathways are responsible for the turning by delivering conditioning (C) pulses to one site and test (T) pulses to the second site, and measuring the frequency of pulse pairs required to evoke a full turn in 10 s. Decreases in the required frequency were usually found at C-T intervals from 0.6 to 1.0 ms, whether the C pulses were delivered to the AMC or to the striatum. This symmetric effect is attributed to collision in fast-conducting axons connecting cortex and striatum. Symmetric collision at C-T intervals of 2–4 ms was observed between cortex and 3 dorsal striatal sites, suggesting slower axons from cortex to these dorsal striatal sites. In several animals, asymmetric changes in required frequency also occurred. When the C pulses were presented via the striatal electrode, the recovery in required frequency occurred at C-T intervals of 1–4 ms, but when the C pulses were presented via the cortical electrode, recovery occurred at C-T intervals of 2–50 ms. This asymmetry is attributed to indirect (i.e., transynaptic) activation of corticostriatal or striatal output axons. These results suggest that in both cortex and striatum there are synapses, transmitting from rostral to caudal, which are important for electrically evoked turning. When C and T pulses were delivered to the same site, decreases in required frequency occurred at C-T intervals from 0.4 to 4 ms, attributable to recovery from refractoriness. In 3 striatal sites, however, large changes were also seen at C-T intervals from 6 to 50 ms. In all 3 sites, asymmetric collision occurred at these same intervals. The recovery at long C-T intervals could be due to transynaptic collision also, resulting from the simultaneous activation of presynaptic and postsynaptic axons by a single striatal electrode. 相似文献
5.
Experiments were carried out to evaluate whether neural activity in the basal ganglia is functionally related to the neural activity underlying mechanisms of theta band oscillation and synchrony in the hippocampal formation. Experiment 1 demonstrated that electrical stimulation administered to the substantia nigra, globus pallidus (GP) and caudate-putamen (CPu) in urethane anesthetized rats elicited theta field activity in the hippocampal formation. Subsequent microinfusion of the local anesthetic procaine hydrochloride into the medial septum reversibly abolished this effect. In Experiment 2, single cell discharge profiles established for 152 cells recorded in nuclei of the basal ganglia resulted in 101 (66%) being classified as theta-related and 51 (34%) classified as nonrelated. Theta-related cells were further subclassified as tonic theta-ON cells (n = 79) and tonic theta-OFF (n = 22). Tonic theta-ON and tonic theta-OFF cells displayed irregular or regular (tonic) discharge patterns. Rhythmic discharge patterns did not occur in any theta-related cells in the nuclei of the basal ganglia. However, analyses using Kaneoke and Vitek's [J. Neurosci. Methods 68, (1996) 211] algorithms revealed that 51/101 (50%) theta-related cells displayed periodicity in their discharge patterns whereas 27/51 (53%) of the nonrelated cells displayed periodicity in their discharge patterns. The periodicities in the majority of cells were in frequency ranges above that of theta band oscillation and synchrony. The results support the following conclusions: (1) the cellular activity of the basal ganglia, composed of nuclei traditionally associated with motor functions, is functionally connected with the neural circuitry involved in the generation of theta band oscillation and synchrony in the hippocampal formation; (2) the observed functional connectivity provides support for the role of the hippocampal formation in sensorimotor integration. 相似文献
6.
RATIONALE: In reaction time (RT) paradigms, in which a variable preparation interval preceded the imperative stimulus, RT become shorter as a function of increasing time from the start of a trial until presentation of the imperative stimulus. The shortening of RT as the preparatory foreperiod elapses reflects increasing motor readiness; however, the underlying neurochemical mechanisms are still poorly defined. OBJECTIVE: The present study investigated in rats whether signals transmitted via the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors and via dopamine D2 receptors in the caudate-putamen (CPu) are involved in motor readiness. METHODS: A simple RT task demanding conditioned lever release was used, in which the upcoming reward magnitude (5 pellets or 1 pellet) was signalled in advance by discriminative stimuli and the imperative stimulus was subsequently presented after a variable foreperiod (200, 500 or 800 ms). RESULTS: In intact rats, RT of conditioned responses was shortened with foreperiod lengthening and with expectancy of the high reward magnitude, but there was no interaction between both factors. Bilateral infusion of the competitive NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV) (2, 10 micrograms in 0.5 microliter/side), of the preferential dopamine D2 antagonist haloperidol (5, 12.5 micrograms in 0.5 microliter/side) or infusion of vehicle (0.5 microliter/side) into the central subregion of the CPu had no effect on progressive RT shortening with increasing foreperiod. CONCLUSION: The present data provide no clues to suggest that motor readiness relies on stimulation of dopamine D2 and NMDA receptors in the central CPu. 相似文献
7.
Mark W Kimpel Wendy N Strother Jeanette N McClintick Lucinda G Carr Tiebing Liang Howard J Edenberg William J McBride 《Alcohol》2007,41(2):95-132
The objective of this study was to determine if there are innate differences in gene expression in selected CNS regions between inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and hippocampus (HIPP) of alcohol-na?ve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray Analysis with a false discovery rate threshold of 0.1, there were 16 genes with differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU, and 21 in the HIPP. When examining the main effect of strain across regions, 296 genes were differentially expressed. Although the relatively small number of genes found significant within individual regions precluded a powerful analysis for over-represented Gene Ontology categories, the much larger list resulting from the main effect of strain analysis produced 17 over-represented categories (P < .05), including axon guidance, gliogenesis, negative regulation of programmed cell death, regulation of programmed cell death, regulation of synapse structure function, and transmission of nerve impulse. Co-citation analysis and graphing of significant genes revealed a network involved in the neuropeptide Y (NPY) transmitter system. Correlation of all significant genes with those located within previously established rat alcohol QTLs revealed that of the total of 313 significant genes, 71 are located within such QTLs. The many regional and overall gene expression differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats. 相似文献
8.
Microdialysis combined with radioimmunoassay was used to measure the release of neurokinin A-like immunoreactivity (NKA-LI) in the rat brain in vivo. The effect of a single dose of amphetamine (2 mg/kg s.c.) on the basal overflow and the potassium-induced release of NKA-LI was assessed in the nucleus accumbens and caudate-putamen. Amphetamine potentiated the potassum-stimulated release of NKA-LI by 71% in the nucleus accumbens, while no significant change was observed in the caudate-putamen. Amphetamine did not affect the basal NKA-LI overflow. 相似文献
9.
大鼠尾壳核微量注射锂盐对痛反应的影响 总被引:1,自引:0,他引:1
本工作利用慢性埋置导管的方法将氯化锂直接注射于大鼠尾壳核头前区及头中心区,在核团水平分析锂盐影响动物痛阈的机制.结果表明:(1)尾壳核头前区注射锂盐可产生明显的镇痛作用,并可分别被纳洛酮、阿托品、酚妥拉明、心得安、荷包牡丹碱和二乙基麦角酰胺所对抗,但不能被氟哌啶醇所阻断.(2)尾壳核头中心区微量注射锂盐不能产生镇痛作用 相似文献
10.
Bombesin microinfusion into the paraventricular nucleus suppresses gastric acid secretion in the rat
Bombesin is a particularly potent inhibitor of gastric acid secretion when injected intracisternally in the rat. Because bombesin-like immunoreactivity is found in several forebrain regions implicated in gut regulation, the ability of bombesin to affect gastric secretion was tested in these areas by direct microinfusion. Bombesin significantly and dose-relatedly suppressed gastric acid secretion when it was infused into the hypothalamic paraventricular nucleus. Bombesin microinfusion into the ventromedial or lateral hypothalamic areas, or the caudate-putamen, had no significant effect. A further experiment using glass micropipets showed that back-diffusion of bombesin along the cannula track to a distant site of action was unlikely to account for the results obtained, and provided further evidence that the active site is limited to the paraventricular nucleus and possibly the ventralmost nucleus reuniens. The results suggest that the bombesin receptors and immunoreactive terminals previously identified in this region may be involved in the central regulation of gastric secretion. 相似文献