Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats

Rumpel, Regina; Alam, Mesbah; Klein, Alexander; Özer, Meltem; Wesemann, Maike; Jin, Xingxing; Krauss, Joachim K.; Schwabe, Kerstin; Ratzka, Andreas; Grothe, Claudia

doi:10.1016/j.nbd.2013.07.016

Cited by 18 publications

(6 citation statements)

References 72 publications

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“…6 Evidence for a hypodopaminergic environment in unilateral Parkinson's disease lesion models show that reduced dopaminergic inputs result in a hypodopaminergic environment and increased post-synaptic striatal D2R expression/ sensitization that mediates rotational behavior when paired with potent D2 agonists like amphetamine. 34 After unilateral CCI, some rats display rotational behavior 2 weeks after amphetamine challenge, 5 supporting the concept of a hypodopaminergic environment, and possibly increased post-synaptic D2R expression, after CCI. In contrast, persistently lower D2R binding occurs in long-term cocaine abusers 35 where reward-like behaviors stimulate DA transmission and result in decreased D2R expression.…”

Section: Discussionmentioning

confidence: 74%

The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB

Wagner

Scanlon

Becker

et al. 2014

J Cereb Blood Flow Metab

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Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [(11)C]βCFT and [(11)C]raclopride. We examined subjects with moderate/severe TBI (N=12) ∼1 year post injury and similarly matched healthy controls (N=13). The variable number of tandem repeat polymorphism within the DAT gene and the TaqI restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.

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Section: Discussionmentioning

confidence: 74%

The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB

Wagner

Scanlon

Becker

et al. 2014

J Cereb Blood Flow Metab

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“…Nevertheless’ recent advances in optogenetic and chemogenetic tools as well as transynaptic labeling (Tønnesen et al, 2011 ; Grealish et al, 2014 ; Torper et al, 2015 ) combined with electrophysiology allows for more delicate measurements of transplants integration in the future. Previous extracellular electrophysiological recordings have shown that dopaminergic fetal neurons partially restore spontaneous neuronal firing in the striatum up to 2 mm from the core of the grafted area (Di Loreto et al, 1996 ; Stromberg et al, 2000 ) and also restore neuronal activity in the subthalamic nucleus (Rumpel et al, 2013 ). Yet only one study has explored the synaptic plasticity in striatal MSNs after fetal cell transplantation (Rylander et al, 2013 ).…”

Section: Synaptic Plasticity After Cell Transplantation In Pdmentioning

confidence: 99%

Striatal Plasticity in L-DOPA- and Graft-Induced Dyskinesia; The Common Link?

Ottosson

Lane

2016

Front. Cell. Neurosci.

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One of the major symptoms of the neurodegenerative condition Parkinson’s disease (PD) is a slowness or loss of voluntary movement, yet frustratingly therapeutic strategies designed to restore movement can result in the development of excessive abnormal movements known as dyskinesia. These dyskinesias commonly develop as a result of pharmacotherapy in the form of L-DOPA administration, but have also been identified following deep brain stimulation (DBS) and intrastriatal cell transplantation. In the case of L-DOPA these movements can be treatment limiting, and whilst they are not long lasting or troubling following DBS, recognition of their development had a near devastating effect on the field of cell transplantation for PD.Understanding the relationship between these therapeutic approaches and the development of dyskinesia may improve our ability to restore function without disabling side effects. Interestingly, despite the fact that dopaminergic cell transplantation repairs many of the changes induced by the disease process and through L-DOPA treatment, there appears to be a relationship between the two. In rodent models of the disease, the severity of dyskinesia induced by L-DOPA prior to the transplantation procedure correlated with post-transplantation, graft-induced dyskinesia. A review of clinical data also suggested that the worse preoperational dyskinesia causes worsened graft-induced dyskinesia (GID). Understanding how these aberrant behaviors come about has been of keen interest to open up these therapeutic options more widely and one major underlying theory is the effects of these approaches on the plasticity of synapses within the basal ganglia. This review uniquely brings together developments in understanding the role of striatal synaptic plasticity in both L-DOPA and GID to guide and stimulate further investigations on the important striatal plasticity.

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“…More recently, striatal dopamine cell transplantation in an animal model of PD also led to restoration of the neuronal firing and oscillations in the SN pars reticulata and STN to normal levels, confirming that continuous DA supply by VM grafts improves not only functional deficits but also rescues basal ganglia electrophysiological activity. 30,31 Other experimental studies have shown that the characteristic increased subthalamic activity found in PD is coupled to abnormally elevated striatal levels of glutamate, which seems to be implicated in the pathogenesis and progression of the disease. 32,33 Other authors have found that STN modulation leads to increased dopamine release in the SN and striatum, 34 which is associated with the concomitant inhibition of pathological neuronal firing 35 and a reduction in striatal glutamate levels.…”

Section: Discussionmentioning

confidence: 99%

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Furlanetti

Cordeiro

et al. 2015

Neurorehabil Neural Repair

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Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson's disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft-host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions.

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Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats

Cited by 18 publications

References 72 publications

The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB

The Influence of Genetic Variants on Striatal Dopamine Transporter and D2 Receptor Binding after TB

Striatal Plasticity in L-DOPA- and Graft-Induced Dyskinesia; The Common Link?

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

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