| Autor: |
Bai-Yun Zeng, Mahmoud M. Iravani, Michael J. Jackson, Sarah Rose, André Parent, Peter Jenner |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 40, Iss 3, Pp 599-607 (2010) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2010.08.004 |
| Popis: |
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. |
| Databáze: |
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| Externí odkaz: |
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