Rationale for targeting the thalamic centre-median parafascicular complex in the surgical treatment of Parkinson's disease

Goff, Lydia Kerkerian‐Le; Jouve, Loreline; Melon, Christophe; Salin, Pascal

doi:10.1016/s1353-8020(09)70807-7

Cited by 22 publications

(10 citation statements)

References 29 publications

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“…In our study naive animals made equivalent numbers (about 50%) of retrievals from both the left or right corridor sides as shown previously by others (Dowd et al, 2005; Fitzsimmons et al, 2006; Döbrössy and Dunnett, 2007; Kerkerian-Le Goff et al, 2009; Jouve et al, 2010). Hemi-PD rats largely neglect sugar pellets encountered on their contralateral side, demonstrating a pronounced ipsilateral retrieval bias (Torres et al, 2008; Cordeiro et al, 2010; Kaindlstorfer et al, 2012; Naughton et al, 2016).…”

Section: Discussionsupporting

confidence: 82%

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Antipova

Holzmann

Schmitt

et al. 2017

Front. Behav. Neurosci.

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Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. The loss of dopaminergic neurons in the substantia nigra leads to a disinhibition of cholinergic interneurons in the striatum. Pharmacotherapeutical strategies of PD-related hypercholinism have numerous adverse side effects. We previously showed that ipsilateral intrastriatal injections of 1 ng in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats inhibit apomorphine-induced rotation behavior significantly up to 6 months. In this study, we extended the behavioral testing of ipsilateral botulinum neurotoxin A (BoNT-A)-injection and additionally investigated the impact of intrastriatal BoNT-A-injections contralateral to the 6-OHDA-lesioned hemisphere on the basal ganglia circuity and motor functions. We hypothesized that the interhemispheric differences of acetylcholine (ACh) concentration seen in unilateral hemi-PD should be differentially and temporally influenced by the ipsilateral or contralateral injection of BoNT-A. Hemi-PD rats were injected with 1 ng BoNT-A or vehicle substance into either the ipsilateral or contralateral striatum 6 weeks after 6-OHDA-lesion and various behaviors were tested. In hemi-PD rats intrastriatal ipsilateral BoNT-A-injections significantly reduced apomorphine-induced rotations and increased amphetamine-induced rotations, but showed no significant improvement of forelimb usage and akinesia, lateralized sensorimotor integration and also no effect on spontaneous locomotor activity. However, intrastriatal BoNT-A-injections contralateral to the lesion led to a significant increase of the apomorphine-induced turning rate only 2 weeks after the treatment. The apomorphine-induced rotation rate decreases thereafter to a value below the initial rotation rate. Amphetamine-induced rotations were not significantly changed after BoNT-A-application in comparison to sham-treated animals. Forelimb usage was temporally improved by contralateral BoNT-A-injection at 2 weeks after BoNT-A. Akinesia and lateralized sensorimotor integration were also improved, but contralateral BoNT-A-injection had no significant effect on spontaneous locomotor activity. These long-ranging and different effects suggest that intrastriatally applied BoNT-A acts not only as an inhibitor of ACh release but also has long-lasting impact on transmitter expression and thereby on the basal ganglia circuitry. Evaluation of changes of transmitter receptors is subject of ongoing studies of our group.

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Section: Discussionsupporting

confidence: 82%

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Antipova

Holzmann

Schmitt

et al. 2017

Front. Behav. Neurosci.

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“…Although this model is known to reflect the major behavioral impairments that are characteristic of PD patients, animal studies are hampered by restrictions on free movement and/or invasive surgery and by short observation periods lasting from a few minutes [35, 49, 51–54] to a number of days [12, 24, 55–57]. To our knowledge, removable and reusable devices have been previously used by only Forni et al [28].…”

Section: Discussionmentioning

confidence: 99%

Deep Brain Stimulation of Hemiparkinsonian Rats with Unipolar and Bipolar Electrodes for up to 6 Weeks: Behavioral Testing of Freely Moving Animals

Badstuebner

Gimsa

Weber

et al. 2017

Parkinson's Disease

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Although the clinical use of deep brain stimulation (DBS) is increasing, its basic mechanisms of action are still poorly understood. Platinum/iridium electrodes were inserted into the subthalamic nucleus of rats with unilateral 6-OHDA-induced lesions of the medial forebrain bundle. Six behavioral parameters were compared with respect to their potential to detect DBS effects. Locomotor function was quantified by (i) apomorphine-induced rotation, (ii) initiation time, (iii) the number of adjusting steps in the stepping test, and (iv) the total migration distance in the open field test. Sensorimotor neglect and anxiety were quantified by (v) the retrieval bias in the corridor test and (vi) the ratio of migration distance in the center versus in the periphery in the open field test, respectively. In our setup, unipolar stimulation was found to be more efficient than bipolar stimulation for achieving beneficial long-term DBS effects. Performance in the apomorphine-induced rotation test showed no improvement after 6 weeks. DBS reduced the initiation time of the contralateral paw in the stepping test after 3 weeks of DBS followed by 3 weeks without DBS. Similarly, sensorimotor neglect was improved. The latter two parameters were found to be most appropriate for judging therapeutic DBS effects.

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“…The functional impact of CM/Pf high-frequency stimulation in parkinsonian and dyskinetic states has been investigated by Lydia Kerkerian-Le Goff’s group using 6-OHDA hemilesioned rats as a model (Jouve et al 2010; Kerkerian-Le Goff et al 2009). Pf-HFS was found to partially ameliorate limb use asymmetry in a test of forelimb hypokinesia while totally reversing lateralized neglect in the so-called corridor test.…”

Section: The Thalamusmentioning

confidence: 99%

“…Pf-HFS reversed the lesion-induced metabolic changes in the STN, GPe, SNr, and partially in the entopeduncular nucleus (i.e., the rodent GPi equivalent). Unlike subthalamic HFS, Pf-HFS did not induce dyskinesias and partially alleviated l -DOPA-induced forelimb dyskinesia (Jouve et al 2010; Kerkerian-Le Goff et al 2009). Taken together, these findings reveal that CM/Pf high-frequency stimulation results in a marked amelioration of sensorimotor integration deficits that are associated with dopaminergic lesions.…”

Section: The Thalamusmentioning

confidence: 99%

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

2018

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With the advent of rodent models of l-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.

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Rationale for targeting the thalamic centre-median parafascicular complex in the surgical treatment of Parkinson's disease

Cited by 22 publications

References 29 publications

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Botulinum Neurotoxin A Injected Ipsilaterally or Contralaterally into the Striatum in the Rat 6-OHDA Model of Unilateral Parkinson’s Disease Differently Affects Behavior

Deep Brain Stimulation of Hemiparkinsonian Rats with Unipolar and Bipolar Electrodes for up to 6 Weeks: Behavioral Testing of Freely Moving Animals

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

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