The effects of reversible inactivation of the subthalamo-pallidal pathway on the behaviour of naive and hemiparkinsonian monkeys

Butler, Ernest; Bourke, Darren W; Finkelstein, David I.; Horne, Malcolm

doi:10.1016/s0967-5868(97)90076-x

Cited by 24 publications

(16 citation statements)

References 54 publications

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“…Recently, contralateral head position has also been reported in monkeys after reversible inactivation of the STN by direct injection of muscimol. This occurred in macaques both with and without prior MPTP‐induced parkinsonism ( Butler et al . 1997 ).…”

Section: Discussionmentioning

confidence: 99%

Behavioural effects of subthalamic nucleus lesions in the hemiparkinsonian marmoset (Callithrix jacchus)

Henderson

Annett

Torres

et al. 1998

Eur J of Neuroscience

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Recent studies in non-human primates support a role for the subthalamic nucleus in the expression of parkinsonian symptomatology, and it has been proposed that subthalamic lesions may provide a surgical treatment for the symptoms of Parkinson's disease in humans. We have applied a broad range of behavioural tests to characterize the effects of lesions of the subthalamic nucleus on parkinsonian symptoms in the unilateral 6-hydroxydopamine (6-OHDA) lesioned marmoset (Callithrix jacchus). Thirteen marmosets were trained on a battery of behavioural tasks that were conducted at regular intervals before and after surgery. All received unilateral 6-OHDA lesions to the medial forebrain bundle. Seven animals were then given an additional N-methyl-D-aspartate lesion of the ipsilateral subthalamic nucleus, whereas the remaining six animals received a variety of control or sham lesions to the nucleus. The 6-OHDA lesions induced a strong ipsilateral bias in head position; mild-moderate ipsilateral rotation spontaneously and after injection of saline or amphetamine; and contralateral rotation after injection of apomorphine. Hemineglect was evident as delayed initiation of reaches on the contralateral side on the staircase reaching task. Additional subthalamic lesions significantly reversed the bias in head position from ipsilateral to contralateral and decreased neglect as evidenced by improved latencies to initiate reaching on the contralateral side at the staircase. However, deficits in skilled movements persisted in the subthalamic nucleus lesion group in that they did not complete the staircase task any faster than the control group and remained impaired on another task which required reaching into tubes. These behavioural effects demonstrate that excitotoxic lesioning of the subthalamic nucleus can ameliorate some, but not all, parkinsonian-like deficits in the unilateral 6-OHDA lesioned marmoset.

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Section: Discussionmentioning

confidence: 99%

Behavioural effects of subthalamic nucleus lesions in the hemiparkinsonian marmoset (Callithrix jacchus)

Henderson

Annett

Torres

et al. 1998

Eur J of Neuroscience

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“…Although the direct injection of KYNA into the globus pallidus internus [243, 244], or its co‐infusion with either QUIN or NMDA into the SNpc [236], resulted in beneficial effects in PD models, the systemic administration of KYNA does not seem to be a good therapeutic approach in CNS disorders for several reasons. It penetrates the blood–brain barrier poorly [118], and it undergoes rapid clearance from the brain and the body, mediated by organic anion transporters [245].…”

Section: Endogenous Neuroprotection In Parkinson’s and Huntington’s Dmentioning

confidence: 99%

Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines

Zádori

Klivényi

Plangár

et al. 2011

Journal of Cellular and Molecular Medicine

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Parkinson’s disease (PD) and Huntington’s disease (HD) are progressive chronic neurodegenerative disorders that are accompanied by a considerable impairment of the motor functions. PD may develop for familial or sporadic reasons, whereas HD is based on a definite genetic mutation. Nevertheless, the pathological processes involve oxidative stress and glutamate excitotoxicity in both cases. A number of metabolic routes are affected in these disorders. The decrease in antioxidant capacity and alterations in the kynurenine pathway, the main pathway of the tryptophan metabolism, are features that deserve particular interest, because the changes in levels of neuroactive kynurenine pathway compounds appear to be strongly related to the oxidative stress and glutamate excitotoxicity involved in the disease pathogenesis. Increase of the antioxidant capacity and pharmacological manipulation of the kynurenine pathway are therefore promising therapeutic targets in these devastating disorders.

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“…In in vivo experiments, the coinfusion of exogenous KYNA with either NMDA or QUIN into the SNpc preserved the activity of striatal tyrosine hydroxylase (probably the most important and rate-limiting enzyme in DA production) (Miranda et al, 1997). The direct injection of KYNA into the globus pallidus internus also resulted in beneficial effects against the toxic effects of MPTP (Graham et al, 1990;Butler et al, 1997). However, the systemic administration of KYNA cannot be selected for therapeutic purposes, as it crosses the BBB poorly (Fukui et al, 1991).…”

Section: Possibility Of Therapeutic Intervention By Modulation Of Thementioning

confidence: 99%

Kynurenines in Parkinson’s disease: therapeutic perspectives

et al. 2011

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Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder the pathomechanism of which is not yet fully known. With regard to the molecular mechanism of development of the disease, oxidative stress/mitochondrial impairment, glutamate excitotoxicity and neuroinflammation are certainly involved. Alterations in the kynurenine pathway, the main pathway of the tryptophan metabolism, can contribute to the complex pathomechanism. There are several possibilities for therapeutic intervention involving targeting of this altered metabolic route. The development of synthetic molecules that would shift the altered balance towards the achievement of neuroprotective effects would be of great promise for future clinical studies on PD.

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The effects of reversible inactivation of the subthalamo-pallidal pathway on the behaviour of naive and hemiparkinsonian monkeys

Cited by 24 publications

References 54 publications

Behavioural effects of subthalamic nucleus lesions in the hemiparkinsonian marmoset (Callithrix jacchus)

Behavioural effects of subthalamic nucleus lesions in the hemiparkinsonian marmoset (Callithrix jacchus)

Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines

Kynurenines in Parkinson’s disease: therapeutic perspectives

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