RESUMEN

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.

Asunto(s)

Adenina/metabolismo , Encéfalo/patología , Líquido Extracelular/metabolismo , Hiperhomocisteinemia/patología , 5'-Nucleotidasa/genética , 5'-Nucleotidasa/metabolismo , Adenosina Difosfato/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/ultraestructura , Modelos Animales de Enfermedad , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Regulación Enzimológica de la Expresión Génica , Hiperhomocisteinemia/metabolismo , Purinas/líquido cefalorraquídeo , ARN Mensajero , Ratas , Ratas Wistar , Fracciones Subcelulares/metabolismo , Fracciones Subcelulares/patología , Sinaptosomas/metabolismo