title: L-DOPA Reverses the Increased Free Amino Acids Tissue Levels Induced by Dopamine Depletion and Rises GABA and Tyrosine in the Striatum.
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.
authors.affiliation: Instituto Cajal, CSIC, Av. Dr. Arce 37, 28002, Madrid, Spain.|CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Solís
authors.affiliation: Instituto Cajal, CSIC, Av. Dr. Arce 37, 28002, Madrid, Spain.|CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: García-Sanz
authors.affiliation: Servicio Neurobiología, Hospital Universitario Ramón y Cajal, IRYCIS, 28034, Madrid, Spain.
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Herranz
authors.affiliation: Servicio Neurobiología, Hospital Universitario Ramón y Cajal, IRYCIS, 28034, Madrid, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Asensio
authors.affiliation: Instituto Cajal, CSIC, Av. Dr. Arce 37, 28002, Madrid, Spain. moratalla@cajal.csic.es.|CIBERNED, Instituto de Salud Carlos III, Madrid, Spain. moratalla@cajal.csic.es.
authors.forename: Rosario
authors.initials: R
authors.lastname: Moratalla
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism; D005552:Forelimb / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D051379:Mice; D016627:Oxidopamine / Q000378:metabolism; D045442:Rotarod Performance Test; D013654:Taurine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D014443:Tyrosine; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D005998:Glycine; D004298:Dopamine
keywords: Abnormal involuntary movements; GABA; Glutamate; Glutamine; Glycine; Parkinson’s disease; Taurine; Tyrosine