title: Serotonergic markers in Parkinson's disease and levodopa-induced dyskinesias.
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.
authors: Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.
authors: Perdita
authors: P
authors: Cheshire
authors: The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
authors: Scott
authors: S
authors: Ayton
authors: Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.|Neurology Department, Alfred Hospital, Melbourne, Australia.
authors: Kelly L
authors: KL
authors: Bertram
authors: Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.
authors: Helen
authors: H
authors: Ling
authors: Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London, UK.
authors: Abi
authors: A
authors: Li
authors: Anatomical Pathology, Alfred Hospital, Melbourne, Australia.
authors: Catriona
authors: C
authors: McLean
authors: Neuroscience Research Australia and University of New South Wales, Sydney, Australia.
authors: Glenda M
authors: GM
authors: Halliday
authors: Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.|Cork University Hospital Neurosciences Department, Cork, Ireland.
authors: Sean S
authors: SS
authors: O'Sullivan
authors: Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London, UK.
authors: Tamas
authors: T
authors: Revesz
authors: The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
authors: David I
authors: DI
authors: Finkelstein
authors: Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.|Neurology Department, Alfred Hospital, Melbourne, Australia.
authors: Elsdon
authors: E
authors: Storey
authors: Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.|Neurology Department, Alfred Hospital, Melbourne, Australia.
authors: David R
authors: DR
authors: Williams
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D065847:Dorsal Raphe Nucleus / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D010300:Parkinson Disease / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D007980:Levodopa; D004298:Dopamine
keywords: Parkinson's disease; dopamine; levodopa-induced dyskinesias; serotonin; striatum