Disease relevance of Subthalamic Nucleus

• Chronic stimulation of subthalamic nucleus improves levodopa-induced dyskinesias in Parkinson's disease [1].
• This indicates that direct effects of deep-brain stimulation of the subthalamic nucleus on levodopa-induced dyskinesias are likely to occur [2].
• The chorea produced by lateral pallidal or medial putaminal injections was virtually indistinguishable from the dyskinesia (chorea/ballism) which has been shown, in previous studies, to be induced by injection of GABA antagonists into the subthalamic nucleus [3].
• The authors report a patient with postischemic parkinsonism who responded neither to levodopa nor to bilateral subthalamic nucleus (STN) stimulation [4].
• In addition to producing rotation, group II and group III metabotropic glutamate receptor agonists induce toxicity in the subthalamic nucleus and overlying thalamus [5].

Psychiatry related information on Subthalamic Nucleus

• Reaction time performance following unilateral striatal dopamine depletion and lesions of the subthalamic nucleus in the rat [6].
• Dyskinesias, such as are observed in Huntington's disease, levodopa-induced dyskinesia and ballism, share mechanistic features in common and are associated with decreased neuronal activity in both the subthalamic nucleus and the medial globus pallidus [7].

High impact information on Subthalamic Nucleus

• To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [8].
• A direct role of dopamine in the rat subthalamic nucleus and an adjacent intrapeduncular area [9].
• 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 [9].
• The increased activity of the subthalamic nucleus (STN) observed has been attributed to a reduction in inhibition mediated by the external segment of the globus pallidus (GPe), secondary to the loss of dopaminergic-neuron influence on D2-receptor-bearing striato-pallidal neurons [10].
• The subthalamic nucleus exerts opposite control on cocaine and 'natural' rewards [11].

Chemical compound and disease context of Subthalamic Nucleus

• The response of subthalamic nucleus neurons to dopamine receptor stimulation in a rodent model of Parkinson's disease [12].
• Lesions of the subthalamic nucleus (STN) have been found to reduce the severe akinetic motor symptom produced in animal models of Parkinson's disease, such as in monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or in monoamine-depleted rats [13].
• We studied 6 advanced-stage Parkinson's disease patients with [18F] fluorodeoxyglucose/positron emission tomography before and 3 months after unilateral ablation of the subthalamic nucleus performed with microelectrode mapping [14].
• Since the substantia nigra compacta receives a moderate glutamatergic innervation from the subthalamic nucleus, we tried to determine whether subthalamic nucleus lesion could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) [15].
• Effects of transient inactivation of the subthalamic nucleus by local muscimol and APV infusions on performance on the five-choice serial reaction time task in rats [16].

Biological context of Subthalamic Nucleus

• Midgestation (e10.5) Pitx2(-/-) embryos have normally formed neural tube structures and cerebral vesicles, whereas older (e14.5) Pitx2(-/-) embryos exhibit loss of gene expression and axonal projections in the subthalamic nucleus (a group of cells in the ventrolateral thalamus) and in the developing superior colliculus of dorsal midbrain [17].
• Whole-cell patch clamp recordings were made from the subthalamic nucleus in rat brain slice preparations to examine the effect of adenosine on inhibitory and excitatory synaptic transmission [18].
• We therefore investigated the potential neuroprotective effects of a preceding subthalamic nucleus lesion on 6-hydroxydopamine (6-OHDA)-induced nigral cell death and compared the retrograde tracer fluorogold (FG) as a marker of cell survival with tyrosinhydroxylase immunoreactivity as a marker of the dopaminergic phenotype [19].
• The present study examined the action of dopamine receptor agonists on c-fos gene expression in the subthalamic nucleus in normal rats [20].
• In a previous analysis of the cortico-basal ganglia circuits, we have shown that a cortical stimulation produces Fos protein expression in the striatum and the subthalamic nucleus, with a pattern which conforms to the anatomical organization of cortical projections [Sgambato V. et al. (1996) Neuroscience 81, 93-112] [21].

Anatomical context of Subthalamic Nucleus

• This ability depends on metabotropic gamma-aminobutyric acid B projections from the external pallidum to subthalamic nucleus and rebound properties of subthalamic cells, as well as on the structure of projections between pallidum and subthalamus [22].
• In the adult rat brain, DuP 753 inhibited radioligand binding to the circumventricular organs and paraventricular nucleus but not to the lateral septum, subthalamic nucleus, and inferior olive [23].
• The effects of subthalamic nucleus lesions alone or in combination with a 6-hydroxydopamine-induced lesion of the substantia nigra were examined in adult rats [24].
• The subthalamic nucleus was the only other basal ganglia structure that expressed mGluR2 [25].
• Substantia nigra neurons possess N-methyl-D-aspartate receptors and there are glutamatergic inputs into the substantia nigra from both the cerebral cortex and the subthalamic nucleus [26].

Associations of Subthalamic Nucleus with chemical compounds

• Cholinergic, GABAergic, and glutamate-enriched inputs from the mesopontine tegmentum to the subthalamic nucleus in the rat [27].
• The reduced severity of LIDs in the absence of subthalamic nucleus stimulation demonstrates that the sensitization phenomenon resulting from long-term intermittent levodopa administration is partially reversible [28].
• Ablation of the subthalamic nucleus supports the survival of nigral dopaminergic neurons after nigrostriatal lesions induced by the mitochondrial toxin 3-nitropropionic acid [29].
• Local field potentials (LFPs) were recorded from adjacent subthalamic nucleus macroelectrode (STNME) contacts simultaneously with EEG activity over the supplementary motor (Cz-FCz) and sensorimotor (C3/4-FC3/4) areas and EMG activity from the contralateral wrist extensors during isometric and phasic wrist movements [30].
• Modifications of local cerebral metabolic rates for glucose and motor behavior in rats with unilateral lesion of the subthalamic nucleus [31].

Gene context of Subthalamic Nucleus

• Two small conductance, calcium-activated potassium channels (SK channels), SK2 and SK3, have been shown to contribute to the afterhyperpolarization (AHP) and to shape the firing behavior in neurons for example in the hippocampal formation, the dorsal vagal nucleus, the subthalamic nucleus, and the cerebellum [32].
• Overall, the ERbeta mRNA hybridization signal was relatively low, but the most abundant ERbeta mRNA areas were the hippocampal formation (primarily the subiculum), claustrum, and cerebral cortex; expression was also present in the subthalamic nucleus and thalamus (ventral lateral nucleus) [33].
• Neuronal staining in the subthalamic nucleus and hypothalamus was predominantly positive for AChE activity [34].
• Parvalbumin and calbindin D-28k in the entopeduncular nucleus, subthalamic nucleus, and substantia nigra of the rat as revealed by double-immunohistochemical methods [35].
• Marked increases in SOD1 (Cu/ZnSOD) activity and glutathione levels were measured within most PSP brain regions examined, whereas, only the subthalamic nucleus exhibited a significant increase (+68%) in SOD2 (MnSOD) activity [36].

Analytical, diagnostic and therapeutic context of Subthalamic Nucleus

• BACKGROUND: High-frequency electrical stimulation of the subthalamic nucleus is a new and highly effective therapy for complications of long-term levodopa therapy and motor symptoms in advanced Parkinson disease (PD) [37].
• The present study shows that treatment with glutamate antagonists, and particularly with AMPA antagonists, alone or in combination with L-DOPA, reverses the overactivity of the subthalamic nucleus and its target areas induced by nigrostriatal denervation [38].
• Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels [39].
• Newer therapies currently in clinical trial include gene therapy to replace lost gamma-aminobutyric acid inputs to the subthalamic nucleus and globus pallidus interna/substantia nigra pars reticulata, and infusion of recombinant glial derived neurotrophic factor to support at-risk nigrostriatal neurons [40].
• Opposite changes, a decrease of the discharge rate of 49% after microinjection of carbachol and an increase of 47% after muscimol, occurred in the contralateral subthalamic nucleus [41].

References