dc.contributor.author |
Fernández-Espejo, E. |
|
dc.contributor.author |
Bis-Humbert, C. |
|
dc.date.accessioned |
2019-11-13T08:37:00Z |
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dc.identifier.uri |
http://hdl.handle.net/11201/150292 |
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dc.description.abstract |
[eng] 3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in cellular, enteric and brain approaches of Parkinsonism in mice. |
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dc.format |
application/pdf |
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dc.relation.isformatof |
Versió postprint del document publicat a: https://doi.org/10.1016/j.neuro.2018.06.002 |
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dc.relation.ispartof |
Neurotoxicology, 2018, vol. 67, p. 178-189 |
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dc.subject.classification |
Ciències de la salut |
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dc.subject.classification |
00 - Ciència i coneixement. Investigació. Cultura. Humanitats |
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dc.subject.other |
Medical sciences |
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dc.subject.other |
00 - Prolegomena. Fundamentals of knowledge and culture. Propaedeutics |
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dc.title |
Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism |
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dc.type |
info:eu-repo/semantics/article |
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dc.type |
info:eu-repo/semantics/acceptedVersion |
|
dc.date.updated |
2019-11-13T08:37:00Z |
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dc.date.embargoEndDate |
info:eu-repo/date/embargoEnd/2026-12-31 |
|
dc.embargo |
2026-12-31 |
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dc.subject.keywords |
3-Iodo-l-tyrosine |
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dc.subject.keywords |
Parkinson |
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dc.subject.keywords |
synuclein |
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dc.subject.keywords |
Tyrosine-hydroxylase |
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dc.subject.keywords |
Nigrostriatal |
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dc.rights.accessRights |
info:eu-repo/semantics/embargoedAccess |
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dc.identifier.doi |
https://doi.org/10.1016/j.neuro.2018.06.002 |
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