Research ArticleParkinson’s Disease

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

Science Translational Medicine  04 Apr 2012:
Vol. 4, Issue 128, pp. 128ra41
DOI: 10.1126/scitranslmed.3003391

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Imaging Cell Therapy in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting about 1 person in every 500 in the United States. A pioneering treatment involving transplantation of dopamine-rich fetal grafts in the brains of patients with PD was initiated nearly 2 decades ago. The goal was to restore dopaminergic neurons in the nigrostriatal pathway that are selectively lost in PD and hence improve motor performance. Although there have been inconsistent results among different trials, some PD patients showed encouraging clinical improvements in motor performance but no improvement in nonmotor symptoms. PD causes not only severe motor symptoms associated with dopamine loss but also nonmotor symptoms such as depression, fatigue, visual hallucinations, and sleep problems that have a significant negative impact on quality of life. Given the importance of nonmotor symptoms in PD, Politis et al. decided to use sophisticated brain imaging techniques to investigate why three PD patients transplanted with fetal grafts 13 to 16 years previously still exhibited nonmotor symptoms even as their motor symptoms improved. When these patients were imaged by positron emission tomography, radioactive tracers that tag dopamine neurons and receptors showed that dopamine neuronal function was restored by the fetal grafts. Also, the principal site of synthesis of another key neurotransmitter, called norepinephrine, was unaffected in these patients. But another scan with an agent that binds to the serotonin transporter and measures the integrity of serotonin-producing neurons showed that there were far fewer serotonin neurons than usual in brain areas related to the regulation of sleep, arousal, feeding, satiety, mood, and emotion. These findings indicate that for more complete, long-term symptomatic relief of both motor and nonmotor symptoms in PD, dopamine neuron replacement with fetal or stem cells will need to be combined with other therapeutic approaches such as additional grafts of serotonin neurons in specific brain areas to relieve nonmotor symptoms by restoring serotonin neurotransmission.