Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson’s Patients with Neural Transplants

Politis, Marios; Wu, Kit; Loane, Clare; Quinn, Niall; Brooks, David J.; Rehncrona, Stig; Björklund, Anders; Lindvall, Olle; Piccini, Paola

doi:10.1126/scitranslmed.3000976

Cited by 294 publications

(296 citation statements)

References 36 publications

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“…4 Recent research indicates that serotonin also plays a crucial role in PD, especially in PD treatment. 5,6 The detection of these two neurotransmitters especially serotonin remains challenging mainly due to their low basal concentrations in the vicinity of neuronal junctions (10 −9 to 10 −6 M). 7 The voltammetric method gains its popularity in detecting oxidizable biogenic amines.…”

Section: * S Supporting Informationmentioning

confidence: 99%

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

et al. 2015

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Ultrasensitive detection and spatially resolved mapping of neurotransmitters, dopamine and serotonin, are critical to facilitate understanding brain functions and investigate the information processing in neural networks. In this work, we demonstrated single molecule detection of dopamine and serotonin using a graphene–Au nanopyramid heterostructure platform. The quasi-periodic Au structure boosts high-density and high-homogeneity hotspots resulting in ultrahigh sensitivity with a surface enhanced Raman spectroscopic (SERS) enhancement factor ∼1010. A single layer graphene superimposed on a Au structure not only can locate SERS hot spots but also modify the surface chemistry to realize selective enhancement Raman yield. Dopamine and serotonin could be detected and distinguished from each other at 10–10 M level in 1 s data acquisition time without any pretreatment and labeling process. Moreover, the heterostructure realized nanomolar detection of neurotransmitters in the presence of simulated body fluids. These findings represent a step forward in enabling in-depth studies of neurological processes including those closely related to brain activity mapping (BAM).

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Section: * S Supporting Informationmentioning

confidence: 99%

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

et al. 2015

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“…It has been found that transplantation of the abovementioned tissue can improve movement related problems in PD patients [38]. In a relevant study, it was found that the motor symptoms can improve even for eighteen years after transplantation [39,40]. In addition, some studies exist which showed contradictory results which oppose the above findings [41,42].…”

Section: Mesencephalic Tissue Of the Human Fetusmentioning

confidence: 64%

The role of cell based therapy in the treatment of Parkinson’s disease

Habibyar¹

2017

J Syst Integr Neurosci

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Parkinson's disease (PD) is considered to be the second common neurodegenerative illness after Alzheimer's disease worldwide. It affects 1-2% of the world population. PD is associated with motor symptoms such as bardykinesia, resting tremor, muscle rigidity. Additionally, non-motor symptoms of PD include sleep disturbance, depression and postural instability. These all PD symptoms are attributed to the selective and progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. A number of pharmacological agents are today available for the treatment of PD. These medications are associated with adverse drug events or lack of efficacy in some patients. Therefore it is required to explore novel methods for the treatment of PD i.e., cell based therapy. A number of cell based therapeutics is tried for the treatment of PD such as embryonic stem cells, induced pluripotent stem cells and somatic stem cells. Although this novel method proved to be effective in PD treatment in animal and clinical studies. But on the other hand it leads to the worsening of the non-motor symptoms. Thus, these studies are not enough, more long term clinical trials are required to proof the efficacy of all aspects of PD through cell based therapy including non-motor symptoms.

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“…Two recent studies [45] of transplanted PD patients have provided support for this idea [46]. These studies included 3 patients who had received fetal mesencephalic grafts 13 to 16 years earlier.…”

Section: Adverse Effects Are Few With Dopaminergic Grafts Except Dysmentioning

confidence: 99%

“…Moreover, several patients whose brains have become available for analysis at autopsy have provided a unique opportunity to study the survival and function of the grafted dopaminergic neurons at survival times for as much as 22 years. Some of these patients, such as the 3 reported in the recent studies [45] and [46] have shown sustained clinical benefit of their transplants for more than 13 years, although in these cases it was associated with the emergence of dyskinesias (GIDs) unrelated to their ongoing medication. The recovery in striatal 18 F-DOPA uptake seen in these patients has been sustained, suggesting that the grafted dopaminergic neurons have survived well over time.…”

Section: Can Neural Grafts Survive and Provide Long-term Function?mentioning

confidence: 99%

Cell Therapeutics in Parkinson's Disease

Lindvall

Björklund

2011

Neurotherapeutics

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The main pathology underlying motor symptoms in Parkinson's disease (PD) is a rather selective degeneration of nigrostriatal dopamine (DA) neurons. Intrastriatal transplantation of immature DA neurons, which replace those neurons that have died, leads to functional restoration in animal models of PD. Here we describe how far the clinical translation of the DA neuron replacement strategy has advanced. We briefly summarize the lessons learned from the early clinical trials with grafts of human fetal mesencephalic tissue, and discuss recent findings suggesting susceptibility of these grafts to the disease process longterm after implantation. Mechanisms underlying graftinduced dyskinesias, which constitute the only significant adverse event observed after neural transplantation, and how they should be prevented and treated are described. We summarize the attempts to generate DA neurons from stem cells of various sources and patient-specific DA neurons from fully differentiated somatic cells, with particular emphasis on the requirements of these cells to be useful in the clinical setting. The rationale for the new clinical trial with transplantation of fetal mesencephalic tissue is described. Finally, we discuss the scientific and clinical advancements that will be necessary to develop a competitive cell therapy for PD patients.

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Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson’s Patients with Neural Transplants

Cited by 294 publications

References 36 publications

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure

The role of cell based therapy in the treatment of Parkinson’s disease

Cell Therapeutics in Parkinson's Disease

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