Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.
NeuroToxicology. 2018-07-01; 67: 178-189
DOI: 10.1016/j.neuro.2018.06.002
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Fernández-Espejo E(1), Bis-Humbert C(2).
Author information:
(1)Laboratorio de Neurofisiología y Neurología Molecular, Departamento de
Fisiología Médica y Biofísica, Universidad de Sevilla, E-41009, Sevilla, Spain.
Electronic address: .
(2)Laboratorio de Neurofisiología y Neurología Molecular, Departamento de
Fisiología Médica y Biofísica, Universidad de Sevilla, E-41009, Sevilla, Spain.
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.
Copyright © 2018 Elsevier B.V. All rights reserved.