Abstract
Perturbations in the cerebral levels of various amino acids are associated with neurological disorders, and previous studies have suggested that such alterations have a role in the motor and non-motor symptoms of Parkinson’s disease. However, the direct effects of chronic L-DOPA treatment, that produces dyskinesia, on neural tissue amino acid concentrations have not been explored in detail. To evaluate whether striatal amino acid concentrations are altered in peak dose dyskinesia, 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian mice were treated chronically with L-DOPA and tissue amino acid concentrations were assessed by HPLC analysis. These experiments revealed that neither 6-OHDA nor L-DOPA treatment are able to alter glutamate in the striatum. However, glutamine increases after 6-OHDA and returns back to normal levels with L-DOPA treatment, suggesting increased striatal glutamatergic transmission with lack of dopamine. In addition, glycine and taurine levels are increased following dopamine denervation and restored to normal levels by L-DOPA. Interestingly, dyskinetic animals showed increased levels of GABA and tyrosine, while aspartate striatal tissue levels are not altered. Overall, our results indicate that chronic L-DOPA treatment, besides normalizing the altered levels of some amino acids after 6-OHDA, robustly increases striatal GABA and tyrosine levels which may in turn contribute to the development of L-DOPA-induced dyskinesia.
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Acknowledgments
This work was supported by Grants from the Spanish Ministerios de Economía y Competitividad (SAF2013-48532-R) and of Sanidad Política Social e Igualdad (ISCIII, CIBERNED CB06/05/0055) and Comunidad de Madrid ref. S2011/BMD-2336 to RM. OS has a CONACYT-Mexico doctoral scholarship. We thank Beatriz Pro and Emilia Rubio for technical assistance.
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Solís, O., García-Sanz, P., Herranz, A.S. et al. L-DOPA Reverses the Increased Free Amino Acids Tissue Levels Induced by Dopamine Depletion and Rises GABA and Tyrosine in the Striatum. Neurotox Res 30, 67–75 (2016). https://doi.org/10.1007/s12640-016-9612-x
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DOI: https://doi.org/10.1007/s12640-016-9612-x