1. Mild hyperhomocysteinemia alters extracellular adenine metabolism in rat brain.
- Author
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Scherer EB, Schmitz F, Vuaden FC, Savio LE, Ferreira AG, Tasca RA, Casali EA, Bogo MR, Bonan CD, and Wyse AT
- Subjects
- 5'-Nucleotidase genetics, 5'-Nucleotidase metabolism, Adenosine Diphosphate metabolism, Adenosine Triphosphatases genetics, Adenosine Triphosphatases metabolism, Adenosine Triphosphate metabolism, Animals, Brain metabolism, Brain ultrastructure, Disease Models, Animal, GPI-Linked Proteins genetics, GPI-Linked Proteins metabolism, Gene Expression Regulation, Enzymologic, Hyperhomocysteinemia metabolism, Purines cerebrospinal fluid, RNA, Messenger, Rats, Rats, Wistar, Subcellular Fractions metabolism, Subcellular Fractions pathology, Synaptosomes metabolism, Adenine metabolism, Brain pathology, Extracellular Fluid metabolism, Hyperhomocysteinemia pathology
- Abstract
Since homocysteine (Hcy) is considered a risk factor to cerebral diseases and adenine nucleotides are important molecules to brain normal function, in the present study we investigated the effect of chronic mild hyperhomocysteinemia on ectonucleotidase activities and expression in rat cerebral cortex. The levels of ATP, ADP, AMP and adenosine (Ado) in cerebrospinal fluid (CSF) of adult rats also were evaluated by high-performance liquid chromatography. For the chronic chemically induced mild hyperhomocysteinemia, Hcy (0.03 μmol/g of body weight) was administered subcutaneously from the 30th to the 60th day of life. Control rats received saline solution in the same volumes. Results showed that Hcy significantly decreased nucleotide hydrolysis in the synaptosomal fraction and increased E-NTPDase1 and ecto-5'-nucleotidase transcripts in rat cerebral cortex. ATP levels were significantly increased, while Ado decreased in CSF of Hcy-treated rats. These findings suggest that the unbalance in ATP and Ado levels may be, at last in part, involved in the cerebral toxicity of mild hyperhomocysteinemia., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2012
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