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Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinson's Patients Treated with Dopamine Grafts

Politis, Marios; Wu, Kit; Loane, Clare; Quinn, Niall P.; Brooks, David J.; Oertel, Wolfgang H.; Björklund, Anders LU ; Lindvall, Olle LU and Piccini, Paola (2012) In Science Translational Medicine 4(128).
Abstract
Cell therapy studies in patients with Parkinson's disease (PD) have been confined to intrastriatal transplantation of dopamine-rich fetal mesencephalic tissue in efforts to improve motor performance. Although some PD patients receiving the dopamine-rich grafts showed improvements in motor symptoms due to replacement of dopaminergic neurons, they still suffered from nonmotor symptoms including depression, fatigue, visual hallucinations, and sleep problems. Using functional imaging and clinical evaluation of motor and nonmotor symptoms in three PD patients transplanted with intrastriatal fetal grafts 13 to 16 years previously, we assessed whether reestablishment of dopaminergic neuronal networks is sufficient to improve a broad range of... (More)
Cell therapy studies in patients with Parkinson's disease (PD) have been confined to intrastriatal transplantation of dopamine-rich fetal mesencephalic tissue in efforts to improve motor performance. Although some PD patients receiving the dopamine-rich grafts showed improvements in motor symptoms due to replacement of dopaminergic neurons, they still suffered from nonmotor symptoms including depression, fatigue, visual hallucinations, and sleep problems. Using functional imaging and clinical evaluation of motor and nonmotor symptoms in three PD patients transplanted with intrastriatal fetal grafts 13 to 16 years previously, we assessed whether reestablishment of dopaminergic neuronal networks is sufficient to improve a broad range of symptoms. At 13 to 16 years after transplantation, dopaminergic innervation was restored to normal levels in basal ganglia and preserved in a number of extrabasal ganglia areas. These changes were associated with long-lasting relief of motor symptoms. Then, we assessed the integrity of their serotonergic and norepinephrine neuronal systems using [C-11]DASB {[C-11]3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile} positron emission tomography (PET) and F-18-dopa PET, respectively. F-18-Dopa uptake in the locus coeruleus was within the normal range. In contrast, [C-11] DASB uptake in the raphe nuclei and regions receiving serotonergic projections was markedly reduced. These results indicate ongoing degeneration of serotonergic raphe nuclei and their projections to regions involved in the regulation of sleep, arousal, feeding, satiety, mood, and emotion. Our findings indicate that future cell-based therapies using fetal tissue or stem cells in PD patients may require additional grafts of serotonergic neurons to relieve nonmotor symptoms by restoring serotonergic neurotransmission in specific cerebral targets. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Translational Medicine
volume
4
issue
128
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • wos:000302732700004
  • scopus:84859496019
ISSN
1946-6242
DOI
10.1126/scitranslmed.3003391
language
English
LU publication?
yes
id
4cc8a40f-c296-4499-8b31-3187598412aa (old id 2574756)
date added to LUP
2012-06-01 08:57:46
date last changed
2017-11-19 03:13:05
@article{4cc8a40f-c296-4499-8b31-3187598412aa,
  abstract     = {Cell therapy studies in patients with Parkinson's disease (PD) have been confined to intrastriatal transplantation of dopamine-rich fetal mesencephalic tissue in efforts to improve motor performance. Although some PD patients receiving the dopamine-rich grafts showed improvements in motor symptoms due to replacement of dopaminergic neurons, they still suffered from nonmotor symptoms including depression, fatigue, visual hallucinations, and sleep problems. Using functional imaging and clinical evaluation of motor and nonmotor symptoms in three PD patients transplanted with intrastriatal fetal grafts 13 to 16 years previously, we assessed whether reestablishment of dopaminergic neuronal networks is sufficient to improve a broad range of symptoms. At 13 to 16 years after transplantation, dopaminergic innervation was restored to normal levels in basal ganglia and preserved in a number of extrabasal ganglia areas. These changes were associated with long-lasting relief of motor symptoms. Then, we assessed the integrity of their serotonergic and norepinephrine neuronal systems using [C-11]DASB {[C-11]3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile} positron emission tomography (PET) and F-18-dopa PET, respectively. F-18-Dopa uptake in the locus coeruleus was within the normal range. In contrast, [C-11] DASB uptake in the raphe nuclei and regions receiving serotonergic projections was markedly reduced. These results indicate ongoing degeneration of serotonergic raphe nuclei and their projections to regions involved in the regulation of sleep, arousal, feeding, satiety, mood, and emotion. Our findings indicate that future cell-based therapies using fetal tissue or stem cells in PD patients may require additional grafts of serotonergic neurons to relieve nonmotor symptoms by restoring serotonergic neurotransmission in specific cerebral targets.},
  author       = {Politis, Marios and Wu, Kit and Loane, Clare and Quinn, Niall P. and Brooks, David J. and Oertel, Wolfgang H. and Björklund, Anders and Lindvall, Olle and Piccini, Paola},
  issn         = {1946-6242},
  language     = {eng},
  number       = {128},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Translational Medicine},
  title        = {Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinson's Patients Treated with Dopamine Grafts},
  url          = {http://dx.doi.org/10.1126/scitranslmed.3003391},
  volume       = {4},
  year         = {2012},
}