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L‐DOPA treatment modulates the expression and activity of L‐aromatic amino acid decarboxylase in the MPTP mouse model
Author(s) -
King Jennifer,
Mackey Veronica R.,
Gladson Muthian,
Charlton Clivel G
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.587.1
Subject(s) - aromatic l amino acid decarboxylase , tyrosine hydroxylase , striatum , dopamine , mptp , hyperkinesia , parkinson's disease , chemistry , dyskinesia , pharmacology , medicine , endocrinology , levodopa , decarboxylase inhibitor , tyrosine , dopaminergic , biochemistry , disease
The replacement of dopamine (DA) with its precursor L‐dopa has remained the most effective symptomatic treatment for Parkinson's disease (PD), although the majority of patients experience a decline in efficacy as well as motor complications after prolonged usage. Although effective, L‐dopa treatment does not restore the physiological levels of DA transmission, and cycles of high and low rates of DA produced can contribute to the pathophysiology of the motor complications that occur. Our results have shown that in the MPTP‐PD mouse model that received sub‐chronic L‐dopa treatments, L‐aromatic amino acid decarboxylase (LAAD), the enzyme that converts L‐dopa to DA, was remarkably reduced in the striatum, and hyperkinesia was observed in the PD model treated with L‐dopa. Striatal tyrosine hydroxylase (TH) expression was decreased in the PD model treated with L‐dopa as well as striatal LAAD activity. DA and its metabolites levels were decreased as well in the PD model treated with L‐dopa along with a decrease in the expression of LAAD. These findings suggest that the loss of efficacy of L‐dopa could possibly be related to the down‐regulation of LAAD that was observed in the striatum, possibly by L‐dopa induced production of dopamine. This observed reduction of LAAD expression and activity is critical in L‐dopa treatment because less DA is synthesized which is needed to counteract the decrease in DA caused by the PD neurodegeneration. Therefore, a greater understanding in the modulation of LAAD could possibly prolong the efficacy of L‐DOPA therapy.