title: Serotonin hyperinnervation of the striatum with high synaptic incidence in parkinsonian monkeys.
abstract: The chronic use of L-Dopa for alleviating the motor symptoms of Parkinson's disease often produces adverse effects such as dyskinesia. Unregulated release of dopamine by serotonin axons following L-Dopa administration is a major presynaptic determinant of these abnormal involuntary movements. The present study was designed to characterize the reorganization of serotonin striatal afferents following dopaminergic denervation in a primate model of Parkinson's disease. Our sample comprised eight cynomolgus monkeys: four that were rendered parkinsonian following MPTP administration and four controls. The state of striatal serotonin and dopamine innervation was evaluated by means of immunohistochemistry with antibodies against serotonin transporter (SERT) and tyrosine hydroxylase. A detailed stereological investigation revealed a significant increase in the number of serotonin axon varicosities in the striatum of MPTP-intoxicated monkeys. This increase is particularly pronounced in the sensorimotor territory of the striatum, where the dopamine denervation is the most severe. Electron microscopic examinations indicate that, in contrast to the nucleus accumbens where the dopamine innervation is preserved, the SERT+ axon varicosities observed in the sensorimotor territory of the putamen establish twice as many synaptic contacts in MPTP-intoxicated monkeys than in controls. These findings demonstrate the highly plastic nature of the serotonin striatal afferent projections, a feature that becomes particularly obvious in the absence of striatal dopamine. Although the number of dorsal raphe serotonin neurons remains constant in parkinsonian monkeys, as shown in the present study, their ascending axonal projections undergo marked proliferative and synaptic adaptive changes that might play a significant role in the potential unregulated and ectopic release of dopamine by serotonin axons after L-Dopa treatment of Parkinson's disease.
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of medicine, Centre de recherche de l'Institut universitaire en santé mentale de Québec, Université Laval, 2601, Canardière, Room F-6500, Quebec City, QC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Gagnon
authors.affiliation: Faculty of Pharmacy, Centre de recherche du CHU de Québec, Université Laval, Quebec City, QC, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Gregoire
authors.affiliation: Faculty of Pharmacy, Centre de recherche du CHU de Québec, Université Laval, Quebec City, QC, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Di Paolo
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of medicine, Centre de recherche de l'Institut universitaire en santé mentale de Québec, Université Laval, 2601, Canardière, Room F-6500, Quebec City, QC, Canada. Martin.Parent@fmed.ulaval.ca.
authors.forename: Martin
authors.initials: M
authors.lastname: Parent
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology*; D065847:Dorsal Raphe Nucleus / Q000378:metabolism / Q000473:pathology; D005260:Female; D008252:Macaca fascicularis; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology; D065842:Pars Compacta / Q000378:metabolism / Q000473:pathology; D059326:Serotonergic Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D014446:Tyrosine 3-Monooxygenase
keywords: Axonal sprouting; Basal ganglia; Dorsal raphe nucleus; Electron microscopy; Primates; Stereology