Graft-mediated functional recovery on a skilled forelimb use paradigm in a rodent model of Parkinson's disease is dependent on reward contingency

Cordeiro, Karina Kohn; Jiang, Wei; Papazoglou, Anna; Tenório, Sérgio Bernardo; Döbrössy, Máté; Nikkhah, Guido

doi:10.1016/j.bbr.2010.04.012

Cited by 19 publications

(11 citation statements)

References 35 publications

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“…However, following transplantation a reduction of the rotational asymmetry was observed on apomorphine injection, as well as the characteristic overcompensation response following amphetamine administration, in all groups. These findings indicate that the transplanted VM cells integrated functionally in the host striatum and produced dopamine, as reported previously (Abrous et al ., ; Hahn et al ., ; Cordeiro et al ., ). However, at 4 weeks post‐graft the STN/ZI‐lesioned group presented a faster and greater reduction in rotational asymmetry following apomorphine administration compared with grafted animals with the MFB only.…”

Section: Discussionmentioning

confidence: 97%

“…Following the induction of anesthesia, the animals were positioned into a rodent stereotactic frame (Stoelting, Germany) and received a complete unilateral lesion of the nigrostriatal dopaminergic pathway induced by a 6‐OHDA (3.6 μg/μL in 0.2% ascorbic acid and 0.9% saline) injection of the right MFB in two tracks (Cordeiro et al ., ). The stereotactically guided injections were performed at the following coordinates in relation to bregma and dura mater (Paxinos & Watson, ).…”

Section: Methodsmentioning

confidence: 97%

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Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

Cordeiro

Furlanetti³

et al. 2014

Eur J of Neuroscience

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Subthalamic nucleus (STN) modulation is currently the gold standard in the treatment of Parkinson's disease (PD) cases refractory to medication. Cell transplantation is a tissue-restorative approach and is a promising strategy in the treatment of PD. One of the obstacles to overcome in cell therapy is the poor dopaminergic cell survival. Our experiment investigates the impact of a partial subthalamotomy prior to ventral mesencephalic (VM) embryonic cell transplantation on dopaminergic cell survival and functional outcome. Unilateral dopamine depletion was carried out in rats, via medial forebrain bundle (MFB) injection of 6-hydroxydopamine, and half of the animals went on to receive unilateral excitotoxic lesions of the STN/Zone Incerta (ZI) causing partial lesion of these structures on the same side as the MFB lesion. All MFB-lesioned animals, with or without the STN/ZI lesion, received striatal ipsilateral embryonic VM cell grafts. The data suggest that the STN/ZI lesion could boost the dopamine cell survival in the grafts by 2.6-fold compared with the control grafted-only group. Moreover, performance on the drug-induced rotation and the spontaneous behavior tests were ameliorated on the STN/ZI-lesioned group to a significantly greater extent than the grafted-only group. These data suggest that the STN/ZI partial lesion optimized the striatal environment, promoting an improvement in cell survival. Further studies are needed to see whether the synergy between STN modulation via deep brain stimulation and cell therapy might have clinical applications in the management of PD.

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Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 97%

Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

Cordeiro

Furlanetti³

et al. 2014

Eur J of Neuroscience

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“…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). As discussed with stepping and cylinder tests, hemi-PD rats showed a severe impairment of motor initiation of the contralateral body including forelimbs and especially in head orientation.…”

Section: Discussionmentioning

confidence: 99%

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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“…Two pellets per step are traditionally used (total 14 pellets per side), but recent data suggest that using four or more pellets per step may yield results with lower variance, depending on the actual construction of the staircase and the depth of the wells (to accommodate the pellets without spillage) (Cordeiro et al, 2010). 4. After a testing period of 15 min, take the rat out of the box.…”

Section: Staircase Testmentioning

confidence: 99%

Analysis of Skilled Forelimb Movement in Rats: The Single Pellet Reaching Test and Staircase Test

Klein

Dunnett

2012

CP Neuroscience

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Brain damage, stroke, and neurodegenerative diseases such as Parkinson's or Huntington's disease can cause severe motor deficits in skilled forelimb use in both humans and rats. These deficits are typically analyzed in a reach-to-eat paradigm. Skilled reaching in rats has been found to be a good model of human skilled reaching. Therefore, rats serve as an excellent tool to monitor the development of deficits after neurological insults or changes after medical intervention. The following protocols comprise two different tests of rat skilled reaching. The single pellet reaching test is a paradigm that involves detailed rating and analysis of qualitative aspects of the reaching movement itself. The staircase test is an objective, high-throughput reaching task that allows reaching success (number of pellets eaten) to be investigated in multiple rats at the same time. Both tests have been used extensively to investigate motor deficits and effects of treatment.

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Graft-mediated functional recovery on a skilled forelimb use paradigm in a rodent model of Parkinson's disease is dependent on reward contingency

Cited by 19 publications

References 35 publications

Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

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

Analysis of Skilled Forelimb Movement in Rats: The Single Pellet Reaching Test and Staircase Test

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