Targeting the subthalamic nucleus in the treatment of Parkinson’s disease

Henderson, James W.; Dunnett, Stephen B.

doi:10.1016/s0361-9230(97)00449-8

Cited by 33 publications

(24 citation statements)

References 59 publications

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“…The STN has been observed to be overactive in animal models of PD (Bergman et al, 1994;Hassani et al, 1996;Nakao et al, 1998). However, Henderson and Dunnett (1998) have questioned the prediction of this model of STN hyperactivity as a result of Parkinsonianinduced GPe disinhibition. They suggest that the reception by the STN of excitatory inputs from the cortex and center medianparafascicular complex of the thalamus and inhibitory inputs from the SN and tegmentum make it possible that PD involves hyperactivity of the STN because of excessive excitatory cortical and parafascicular thalamic input and decreased inhibitory nigral and tegmental input to the STN.…”

Section: Discussionmentioning

confidence: 99%

“…The STN is being increasingly recognized as having a central role in basal ganglia physiology and PD pathophysiology (Henderson and Dunnett, 1998). Decreased dopamine levels in the ST are thought to alter striatal function, including reduced activity of GABA/substance P/dynorphin medium spiny neurons and reduced inhibition of GABA/enkephalin medium spiny neurons, which render the globus pallidus pars externus (GPe) hypoactive by provoking excessive inhibition (Rodriguez et al, 1998).…”

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confidence: 99%

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Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants

et al. 2001

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One of the critical variables that influences the efficacy of clinical neural transplantation for Parkinson's disease (PD) is optimal graft placement. The current transplantation paradigm that focuses on ectopic placement of fetal grafts in the striatum (ST) fails to reconstruct the basal ganglia circuitry or normalize neuronal activity in important basal ganglia structures, such as the substantia nigra (SN) and the subthalamic nucleus (STN). The aim of this study was to investigate a multitarget neural transplantation strategy for PD by assessing whether simultaneous dopaminergic transplants in the ST, SN, and STN induce functional recovery in hemiparkinsonian rats. Forty-six female Wistar rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were randomly divided into eight groups and received lesions only or injections of 900,000 embryonic rat ventral mesencephalic cells in the (1) ST, (2) SN, (3) STN, (4) ST and SN, (5) ST, SN, and STN, (6) ST and STN, or (7) SN and STN. The number of cells transplanted was equally divided among grafting sites. Animals with two grafts received 450,000 cells in each structure, and animals with three grafts received 300,000 cells per structure. Recovery was assessed by amphetamine-induced rotations and the stepping tests. Graft survival was assessed using tyrosine hydroxylase immunohistochemistry. At 8 weeks after transplantation, simultaneous dopaminergic transplants in the ST, SN, and STN induced significant improvement in rotational behavior and stepping test scores. Intrastriatal transplants were associated with significant recovery of rotational asymmetry, whereas SN and STN transplants were associated with improved forelimb function scores. These results suggest that restoration of dopaminergic activity to multiple basal ganglia targets, such as the ST and SN, or the ST and STN, promotes a more complete functional recovery of complex sensorimotor behaviors. A multitarget transplant strategy aimed at optimizing dopaminergic reinnervation of the basal ganglia may be crucial in improving clinical outcomes in PD patients.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants

et al. 2001

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“…Thalamic 5-[ 125 I]-A-85380 binding in PD also tended to be lower than in DLB, with significance reached in the STH nucleus. Dopamine deficiency in PD causes the disinhibition and overactivity of the STH nucleus and its projections to the internal GP, which in turn overinhibits thalamocortical projections which is thought to be responsible for the appearance of symptoms such as akinesia, rigidity, and perhaps tremor (Henderson and Dunnett, 1998) , and PD and in the substantia nigra in DLB and PD differentiates these groups from VaD as well as controls. This could be valuable in differentiating VaD from primary degenerative dementia.…”

Section: Disease Comparisonsmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380

Pimlott

Piggott

Owens

et al. 2003

Neuropsychopharmacol

152

105

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“…The goal of DBS of the subthalamic nucleus is to inactivate inhibitory function thereby allowing the remaining pathways to function, despite reduced activation from the degenerated substantia nigra (McIntyre, Savasta, Kerkerian-Le Goff, & Vitek, 2004; Trost et al, 2006). Despite great success in reducing tremor, rigidity, and hypokinesia (Henderson & Dunnett, 1998), there may be a disconnect between positive outcomes for speech and nonspeech movements (see Kent et al, 2001). Clinical anecdotes, preliminary evidence, and patient reports suggest speech may not improve or may even worsen post-DBS in some people.…”

Section: Introductionmentioning

confidence: 99%

The role of subcortical structures in recited speech: Studies in Parkinson's disease

Bridges

Sidtis

2013

Journal of Neurolinguistics

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The role of subcortical structures in language function is complex and dependent on language task, with studies increasingly showing subcortical involvement for the production of formulaic language, including recited speech. Individuals with Parkinson's disease (PD), with (n = 6) and without (n = 7) surgical treatment, deep brain stimulation (DBS), were compared to healthy adults (n = 14) to determine whether individuals with subcortical dysfunction produce more errors during a recitation speech task. Participants were asked to recite poems, prayers, and rhymes familiar to them in order to determine the effects of subcortical disease on recited speech ability. When compared with healthy controls, the DBS-OFF group produced significantly more error words, suggesting that deficits in recitation arise with severe states of subcortical dysfunction. Individuals with DBS in the ON or OFF conditions did not differ significantly during the recited speech task. Results support a model of language where large units of overlearned language are at least partially modulated by subcortical structures.

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Targeting the subthalamic nucleus in the treatment of Parkinson’s disease

Cited by 33 publications

References 59 publications

Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants

Enhancement of Sensorimotor Behavioral Recovery in Hemiparkinsonian Rats with Intrastriatal, Intranigral, and Intrasubthalamic Nucleus Dopaminergic Transplants

Nicotinic Acetylcholine Receptor Distribution in Alzheimer's Disease, Dementia with Lewy Bodies, Parkinson's Disease, and Vascular Dementia: In Vitro Binding Study Using 5-[125I]-A-85380

The role of subcortical structures in recited speech: Studies in Parkinson's disease

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