1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced acute transient dystonia in monkeys associated with low striatal dopamine

Tabbal, Samer D.; Mink, Jonathan W.; Antenor, Jo Ann V.; Carl, Juanita L.; Moerlein, Stephen M.; Perlmutter, Joel S.

doi:10.1016/j.neuroscience.2006.04.072

Cited by 60 publications

(92 citation statements)

References 39 publications

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“…The delayed onset of abnormal beta oscillations in the 6-OHDA-lesioned rat model of PD may have behavioral parallels in other PD models, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Early motor deficits after acute MPTP toxicity are often dystonic in nature, whereas classic Parkinsonism may be delayed by one or more weeks after intoxication (Tabbal et al, 2006). This natural history is consistent with clinical experience: acute exposure to dopamine receptor antagonists may cause dystonia and related dyskinesias, but Parkinsonism requires more chronic neuroleptic use (Ayd, 1961).…”

Section: Discussionmentioning

confidence: 58%

Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex

Mallet¹,

Pogosyan²,

Sharott³

et al. 2008

J. Neurosci.

425

469

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In the subthalamic nucleus (STN) of Parkinson's disease (PD) patients, a pronounced synchronization of oscillatory activity at beta frequencies (15-30 Hz) accompanies movement difficulties. Abnormal beta oscillations and motor symptoms are concomitantly and acutely suppressed by dopaminergic therapies, suggesting that these inappropriate rhythms might also emerge acutely from disrupted dopamine transmission. The neural basis of these abnormal beta oscillations is unclear, and how they might compromise information processing, or how they arise, is unknown. Using a 6-hydroxydopamine-lesioned rodent model of PD, we demonstrate that beta oscillations are inappropriately exaggerated, compared with controls, in a brain-state-dependent manner after chronic dopamine loss. Exaggerated beta oscillations are expressed at the levels of single neurons and small neuronal ensembles, and are focally present and spatially distributed within STN. They are also expressed in synchronous population activities, as evinced by oscillatory local field potentials, in STN and cortex. Excessively synchronized beta oscillations reduce the information coding capacity of STN neuronal ensembles, which may contribute to parkinsonian motor impairment. Acute disruption of dopamine transmission in control animals with antagonists of D 1 /D 2 receptors did not exaggerate STN or cortical beta oscillations. Moreover, beta oscillations were not exaggerated until several days after 6-hydroxydopamine injections. Thus, contrary to predictions, abnormally amplified beta oscillations in cortico-STN circuits do not result simply from an acute absence of dopamine receptor stimulation, but are instead delayed sequelae of chronic dopamine depletion. Targeting the plastic processes underlying the delayed emergence of pathological beta oscillations after continuing dopaminergic dysfunction may offer considerable therapeutic promise.

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Section: Discussionmentioning

confidence: 58%

Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex

Mallet¹,

Pogosyan²,

Sharott³

et al. 2008

J. Neurosci.

425

469

View full text Add to dashboard Cite

show abstract

“…A link between striatal dopamine depletion and the development of dystonia is also suggested by the observation that dystonia can occur as a transient phenomenon in MPTPtreated monkeys before the animals develop overt Parkinsonism (Perlmutter et al, 1997a,b;Tabbal et al, 2006). PET measurements of [ 18 F]-DOPA uptake have directly demonstrated that striatal dopaminergic activity was reduced at the time at which dystonia was present in these animals (Tabbal et al, 2006).…”

Section: The Role Of Dopamine In Dystoniamentioning

confidence: 98%

“…PET measurements of [ 18 F]-DOPA uptake have directly demonstrated that striatal dopaminergic activity was reduced at the time at which dystonia was present in these animals (Tabbal et al, 2006). Given the evidence for dopaminergic dysfunction, it is instructive to consider the similarities and differences between dystonia and Parkinson's disease.…”

Section: The Role Of Dopamine In Dystoniamentioning

confidence: 99%

Commentary: Dopaminergic dysfunction in DYT1 dystonia

Wichmann

2008

Experimental Neurology

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A three-base-pair deletion in the torsinA gene leads to generalized torsion dystonia (DYT1) in humans, an often devastating movement disorder in which voluntary movements are disrupted by sustained muscle spasms and abnormal limb posturing. In a recent issue of Experimental Neurology, Zhao et al. (2008) have provided a thorough behavioral, anatomic, and biochemical characterization of a mouse line that over-expresses human mutant torsinA, with particular emphasis on the possible role of dopaminergic dysfunction in these animals. This commentary provides an overview of the clinical and genetic features of the human disease and of the available transgenic mouse models for DYT1 dystonia, and discusses the evidence favoring the role of dopamine in the clinical manifestations of the disease.

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“…Thus, dystonia may develop either acutely or delayed (tardive dystonia), in normal individuals treated with dopamine-receptor blocking agents, or can be a sign of other diseases with disturbed dopamine metabolism, such as PD, levodopa-responsive dystonia, or DYT1 [184][185][186][187][188][189]. Transient dystonia has also been observed in monkeys treated with the dopaminergic neurotoxin MPTP [190][191][192].…”

Section: Dystoniamentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced acute transient dystonia in monkeys associated with low striatal dopamine

Cited by 60 publications

References 39 publications

Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex

Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex

Commentary: Dopaminergic dysfunction in DYT1 dystonia

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

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