The Hydrolysis of Striatal Adenine- and Guanine-Based Purines in a 6-Hydroxydopamine Rat Model of Parkinson’s Disease

Autor: Ana Elisa Böhmer, João José Freitas Sarkis, Alcyr Alves de Oliveira, Diogo O. Souza, Maurício Reis Bogo, Cristiane Batassini, Tadeu Mello e Souza, Daniela Pochmann, Jean Pierre Oses, Luis Valmor Cruz Portela, Carla Denise Bonan, Fernanda Cenci Vuaden, Roberta Bristot Silvestrin
Rok vydání: 2010
Předmět:
Zdroj: Repositório Institucional PUCRS
Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
instacron:PUC_RS
ISSN: 1573-6903
0364-3190
DOI: 10.1007/s11064-010-0305-1
Popis: Parkinson's disease (PD) is characterized by a progressive neurodegeneration in the substantia nigra and a striatal dopamine decrease. Striatal extracellular adenosine and ATP modulate the dopaminergic neurotransmission whereas guanosine has a protective role in the brain. Therefore, the regulation of their levels by enzymatic activity may be relevant to the clinical feature of PD. Here it was evaluated the extracellular nucleotide hydrolysis from striatal slices 4 weeks after a unilateral infusion with 6-OHDA into the medial forebrain bundle. This infusion increased ADP, AMP, and GTP hydrolysis by 15, 25, and 41%, respectively, and decreased GDP hydrolysis by 60%. There was no change in NTPDases1, 2, 3, 5, 6, and 5'-nucleotidase transcription. Dopamine depletion changes nucleotide hydrolysis and, therefore, alters the regulation of striatal nucleotide levels. These changes observed in 6-OHDA-lesioned animals may contribute to the symptoms observed in the model and provide evidence to indicate that extracellular purine hydrolysis is a key factor in understanding PD, giving hints for new therapies.
Databáze: OpenAIRE
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