Morphological changes in serotoninergic neurites in the striatum and globus pallidus in levodopa primed MPTP treated common marmosets with dyskinesia.
Hyperinnervation of the striatum by serotoninergic (5-HT) terminals occurs after destruction of the dopaminergic nigro-striatal pathway. Recent studies have suggested that non-physiological release of dopamine (DA) formed from levodopa in these serotoninergic terminals underlies abnormal involuntary movement (AIMs) induction in 6-OHDA lesioned rats. In the present study, we used tryptophan hydroxylase (TPH) immunohistochemistry to determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment and the induction of dyskinesia by levodopa alter the morphology of 5-HT fibres in the striatum of common marmosets. The caudate-putamen of normal monkeys contained numerous fine and smooth TPH positive fibres and numerous varicose fibres, but a marked hyperinnervation of TPH positive fibres characterised by a significant increase in the number and diameter of TPH positive axon varicosities was noted in the dorsal caudate and putamen of MPTP-intoxicated monkeys but not the globus pallidus. In MPTP-intoxicated marmosets that had received chronic levodopa treatment to induce dyskinesia, a further increase in the number and enlargement of TPH positive axonal varicosities in both caudate nucleus and putamen was evident. Following LID induction, a similar pattern of increase was also observed in the external segment of the globus pallidus, but only a significant varicosity enlargement was seen in the internal pallidal segment. These results confirm that striatal 5-HT hyperinnervation follows nigro-striatal pathway loss and provide the first evidence in primates that chronic levodopa treatment and the onset of dyskinesia are associated with a marked hypertrophy of striatal 5-HT axonal varicosities. These findings support the concept that altered 5-HT function may contribute to the genesis or expression of LID.
Zeng
Bai-Yun
BY
NDRG, School of Biomedical and Health Sciences, King's College, London, UK.
Iravani
Mahmoud M
MM
Jackson
Michael J
MJ
Rose
Sarah
S
Parent
André
A
Jenner
Peter
P
D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity*; D002144:Callithrix; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004409:Dyskinesia, Drug-Induced / Q000473:pathology*; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects / Q000473:pathology*; D007150:Immunohistochemistry; D007980:Levodopa / Q000633:toxicity*; D008297:Male; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000473:pathology*; D012701:Serotonin / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D000978:Antiparkinson Agents; D012701:Serotonin; D007980:Levodopa; D014365:Tryptophan Hydroxylase