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1.
Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity 总被引：23，自引：0，他引：23
The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine. 相似文献
2.
Maret S Franken P Dauvilliers Y Ghyselinck NB Chambon P Tafti M 《Science (New York, N.Y.)》2005,310(5745):111-113
Delta oscillations, characteristic of the electroencephalogram (EEG) of slow wave sleep, estimate sleep depth and need and are thought to be closely linked to the recovery function of sleep. The cellular mechanisms underlying the generation of delta waves at the cortical and thalamic levels are well documented, but the molecular regulatory mechanisms remain elusive. Here we demonstrate in the mouse that the gene encoding the retinoic acid receptor beta determines the contribution of delta oscillations to the sleep EEG. Thus, retinoic acid signaling, which is involved in the patterning of the brain and dopaminergic pathways, regulates cortical synchrony in the adult. 相似文献
3.
Dissociated cell suspensions, prepared from the substantia nigra and septal regions of rat embryos, can be grafted to the depths of the caudate-putamen and hippocampus of aged rats. The grafts were rich in dopamine-containing and acetylcholinesterase-positive neurons and had produced extensive new dopaminergic and cholinergic terminal networks in the host neostriatum and hippocampus, respectively. The intrastriatal dopaminergic grafts were associated with a significant improvement in motor coordination in the aged rats. This result suggests that the intracerebral grafting technique may provide a new tool for exploring the role of dopaminergic and cholinergic deficits in the neurological and behavioral impairments associated with aging. 相似文献
4.
有机磷农药神经发育毒性作用机制研究进展 总被引：4，自引：0，他引：4
有机磷农药是目前使用最为广泛的一种化学合成杀虫剂,它所引起的毒性作用已成为全球关注的公共卫生问题.研究表明,有机磷农药的神经发育毒性作用主要与其不可逆地抑制乙酰胆碱酯酶进而导致乙酰胆碱在突触处的积累有关.而最近也提出了有机磷农药的其他非胆碱酯酶作用机制,这些作用机制涉及兴奋性氨基酸递质系统、多巴胺能神经递质系统、五羟色胺递质系统、cAMP反应单元结合蛋白信号通路和氧化应激等.针对有机磷农药神经发育毒性作用机制的研究现状进行综述. 相似文献
5.
Refojo D Schweizer M Kuehne C Ehrenberg S Thoeringer C Vogl AM Dedic N Schumacher M von Wolff G Avrabos C Touma C Engblom D Schütz G Nave KA Eder M Wotjak CT Sillaber I Holsboer F Wurst W Deussing JM 《Science (New York, N.Y.)》2011,333(6051):1903-1907
The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioral adaptation to stress and is causally linked to emotional disorders. Using neurochemical and genetic tools, we determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid-containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders. 相似文献
6.
A major direct GABAergic pathway from zona incerta to neocortex 总被引：4，自引：0，他引：4
Retrograde fluorescent tracers were used to demonstrate a previously unknown but sizable direct gamma-aminobutyric acid (GABA)-containing neuronal pathway from the zona incerta to the neocortex in rats. This incertocortical pathway was found to project bilaterally to the entire neocortex and exhibited a rough corticotopic organization. Many of the zona incerta neurons projecting to the parietal and occipital cortices could also be immunohistochemically stained with antibodies to glutamic acid decarboxylase and GABA. Few of these neurons were immunoreactive to tyrosine hydroxylase antibodies, which identify dopamine-containing neurons. Injections in the frontal and entorhinal cortices labeled many neurons near or within the dopaminergic A13 subdivision of the zona incerta. In addition, the incertocortical system was found to be significantly larger during early postnatal (2 to 3 weeks) development. The projection pattern of this newly discovered pathway resembles that of the monoaminergic and cholinergic systems, arising from the brainstem and forebrain, suggesting possible similarities of function. 相似文献
7.
Long-term treatment with lithium prevents the development of dopamine receptor supersensitivity 总被引：9，自引：0，他引：9
Long-term treatment of rats with haloperidol produced an increased sensitivity to the locomotor and stereotypic effect of apomorphine. This behavioral dopaminergic supersensitivity was accompanied by increased binding of [3H] spiroperidol in the striatum. Rats treated concurrently with lithium and haloperidol failed to develop both behavioral sensitivity to apomorphine and increased striatal dopamine receptor binding. The ability of lighium to prevent recurrent manicdepressive episodes may be related, in part, to its ability to stabilize dopaminergic receptor sensitivity. 相似文献
8.
Valente EM Abou-Sleiman PM Caputo V Muqit MM Harvey K Gispert S Ali Z Del Turco D Bentivoglio AR Healy DG Albanese A Nussbaum R González-Maldonado R Deller T Salvi S Cortelli P Gilks WP Latchman DS Harvey RJ Dallapiccola B Auburger G Wood NW 《Science (New York, N.Y.)》2004,304(5674):1158-1160
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD. 相似文献
9.
Parkinson's disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila melanogaster upon directed expression of alpha-synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a major component of proteinaceous Lewy bodies. We report that directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with alpha-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated alpha-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression. 相似文献
10.
【目的】明确印楝素是否能诱导果蝇产生厌恶性味觉记忆,并探讨多巴胺信号在这种记忆形成中的调控作用。【方法】利用印楝素诱导果蝇产生短期厌恶性味觉记忆,并通过昆虫口器伸展反应测试诱导结果;采用压力注射给药方式及果蝇全脑膜片钳记录,研究印楝素对果蝇脑内不同亚群多巴胺能神经元兴奋性及受体电流的影响。【结果】印楝素A及印楝素干粉均能显著抑制果蝇口器伸展的概率,口器伸展反应(PER)分别为60.34%和17.24%,(P0.007),并且干粉的效果更加明显;印楝素对不同亚群的多巴胺能神经元的兴奋性有不同的作用,PPL1、PAM和PPM2亚群兴奋性呈现增加趋势,其中PPL1亚群兴奋性改变最为显著;印楝素对多巴胺D1受体具有激动效应,这种激动效应可被D1受体特异性拮抗剂抑制。【结论】印楝素可以诱导果蝇产生厌恶性味觉记忆,这种记忆受果蝇脑内多巴胺能信号的调控。 相似文献
11.
Drosophila melanogaster can make appropriate choices among alternative flight options on the basis of the relative salience of competing visual cues. We show that this choice behavior consists of early and late phases; the former requires activation of the dopaminergic system and mushroom bodies, whereas the latter is independent of these activities. Immunohistological analysis showed that mushroom bodies are densely innervated by dopaminergic axons. Thus, the circuit from the dopamine system to mushroom bodies is crucial for choice behavior in Drosophila. 相似文献
12.
Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system 总被引：27，自引：0，他引：27
M J Perlow W J Freed B J Hoffer A Seiger L Olson R J Wyatt 《Science (New York, N.Y.)》1979,204(4393):643-647
In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue. 相似文献
13.
A MicroRNA feedback circuit in midbrain dopamine neurons 总被引：4，自引：0，他引：4
Kim J Inoue K Ishii J Vanti WB Voronov SV Murchison E Hannon G Abeliovich A 《Science (New York, N.Y.)》2007,317(5842):1220-1224
14.
Widespread distribution of brain dopamine receptors evidenced with [125I]iodosulpride, a highly selective ligand 总被引：10，自引：0，他引：10
M P Martres M L Bouthenet N Sales P Sokoloff J C Schwartz 《Science (New York, N.Y.)》1985,228(4700):752-755
The new benzamide derivative [125I]iodosulpride is a highly sensitive and selective ligand for D-2 dopamine receptors and displays a very low nonspecific binding to membrane or autoradiographic sections. On autoradiographic images, D-2 receptors are present not only in well-established dopaminergic areas but also, in a discrete manner, in a number of catecholaminergic regions in which the dopaminergic innervation is still unknown, imprecise, or controversial, as in the sensorimotor cerebral cortex or cerebellum. This widespread distribution suggests larger physiological and pathophysiological roles for cerebral dopamine receptors than was previously thought. 相似文献
15.
Bäckman L Nyberg L Soveri A Johansson J Andersson M Dahlin E Neely AS Virta J Laine M Rinne JO 《Science (New York, N.Y.)》2011,333(6043):718
Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory. 相似文献
16.
Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders 总被引：1，自引：0，他引：1
Masliah E Rockenstein E Veinbergs I Mallory M Hashimoto M Takeda A Sagara Y Sisk A Mucke L 《Science (New York, N.Y.)》2000,287(5456):1265-1269
To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions. 相似文献
17.
A direct role of dopamine in the rat subthalamic nucleus and an adjacent intrapeduncular area 总被引：2，自引：0，他引：2
L L Brown M H Markman L I Wolfson B Dvorkin C Warner R Katzman 《Science (New York, N.Y.)》1979,206(4425):1416-1418
The subthalamic nucleus, a clinically important component of the extrapyramidal motor system, and a lateral area extending into the peduncle contain catecholamine terminals and dopamine receptors coupled to adenylate cyclase. In addition, dopamine agonists administered in vivo enhance glucose utilization in the region. Thus, neuronal function in this region is directly affected by dopamine and dopaminergic drugs. 相似文献
18.
Tetrahydrobiopterin in striatum: localization in dopamine nerve terminals and role in catecholamine synthesis 总被引：16，自引：0，他引：16
The hydroxylase cofactor, tetrahydrobiopterin, and its biosynthetic system are localized in dopaminergic nerve terminals in the striatum. This conclusion is based on the nearly equivalent loss of tyrosine hydroxylase and tetrahydrobiopterin and its initial biosynthetic enzyme, guanosine triphosphate cyclohydrolase, after injection of 6-hydroxydopamine into the substantia nigra. The role of the hydroxylase cofactor in the regulation of dopamine synthesis is reassessed. 相似文献
19.
Dopaminergic terminals in the rat cortex 总被引：15，自引：0，他引：15
The destruction of ascending noradreniergic pathways by bilateral microinjections of 6-hydroxydopamnine made laterally to the pedunculus cerebellaris superior completely abolished the in vitro synthesis of [(3)H]norepinephrine from L-[(3)H]tyrosine in slices and in synaptosomes of the rat cortex. However, normal [(3)H]dopamine synthesis could still be observed in both cortical preparations from animals with lesions. These results provide the first biochemical support for the existence of dopaminergic terminals independent of noradrenergic terminals in the rat cortex. 相似文献
20.
In otherwise profoundly akinetic rats that had been severely depleted of brain catecholamines, anticholinergic drugs caused excessive walking. The effect did not appear until 10 days after surgery and then increased with time, suggesting that a phenomenon analogous to denervation supersensitivity may be involved. If the animals walked into corners, they were unable to turn around or back out. Their gait (extremely short steps) was reminiscent of that of patients with Parkinson's disease. The results are consistent with a mutually antagonistic interaction between cholinergic and dopaminergic brain systems and emphasize certain complexities in this interaction. 相似文献