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Mov Disord. 2015 May;30(6):796-804. doi: 10.1002/mds.26144. Epub 2015 Feb 4.

Serotonergic markers in Parkinson's disease and levodopa-induced dyskinesias.

Author information

1
Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.
2
The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
3
Neurology Department, Alfred Hospital, Melbourne, Australia.
4
Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.
5
Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London, UK.
6
Anatomical Pathology, Alfred Hospital, Melbourne, Australia.
7
Neuroscience Research Australia and University of New South Wales, Sydney, Australia.
8
Cork University Hospital Neurosciences Department, Cork, Ireland.

Abstract

Preclinical animal models implicate serotonin neurons in the pathophysiology of levodopa (l-dopa)-induced dyskinesias in Parkinson's disease (PD), but effective treatment remains elusive. We examined the relationship between serotonin and l-dopa-induced dyskinesias in a pathologically confirmed cohort of PD patients. We obtained brain tissue from 44 PD cases and 17 age-matched controls and assessed monoamine levels and the serotonin and dopamine transporters in the striatum, and the extent of dopaminergic and serotonergic cell preservation in the substantia nigra (SN) and the dorsal raphe nuclei (DRN), respectively. As expected, PD patients demonstrated a severe loss of all dopaminergic markers, including dopamine (P < 0.0001) and the dopamine transporter (P < 0.0001) in the striatum, and dopaminergic neurons (P < 0.001) in the SN, compared with controls. Marked serotonin loss was observed in the caudate (but not putamen) in PD patients compared with controls (P < 0.001), but no difference was found in the levels of the serotonin transporter in the striatum or density of serotonergic neurons in the DRN between these groups, suggesting a functional but not structural change in the serotonergic system in PD. No difference was seen in levels of serotonergic and dopaminergic markers in the striatum between PD patients with and without dyskinesias, or between cases separated according to the clinical severity of their dyskinesias. The absence of a correlation between striatal serotonin markers and the incidence and severity of l-dopa-induced dyskinesias suggests that an intact and functioning serotonergic system is not a risk factor for developing dyskinesias in PD.

KEYWORDS:

Parkinson's disease; dopamine; levodopa-induced dyskinesias; serotonin; striatum

PMID:
25649148
DOI:
10.1002/mds.26144
[Indexed for MEDLINE]

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