Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 [¹¹C]DASB {[¹¹C]3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile} positron emission tomography (PET) and ¹⁸F-dopa PET, respectively. ¹⁸F-dopa uptake in the locus coeruleus was within the normal range. In contrast, [¹¹C]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.

Original publication

DOI

10.1126/scitranslmed.3003391

Type

Journal article

Journal

Sci Transl Med

Publication Date

04/04/2012

Volume

4

Keywords

Aged, Dopamine, Dopaminergic Neurons, Female, Humans, Male, Middle Aged, Nerve Degeneration, Neurons, Parkinson Disease, Serotonergic Neurons