Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neuroscience. 2012 Oct 25;223:28-34. doi: 10.1016/j.neuroscience.2012.07.035. Epub 2012 Aug 1.
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.
由于同型半胱氨酸（Hcy）被认为是引起脑部疾病的一个危险因素，而腺嘌呤核苷酸是大脑正常功能的重要分子，因此本研究旨在探讨慢性轻度高同型半胱氨酸血症对大鼠大脑皮质外核苷酸酶活性和表达的影响。我们还通过高效液相色谱法评估了成年大鼠脑脊液（CSF）中 ATP、ADP、AMP 和腺苷（Ado）的水平。对于慢性化学诱导的轻度高同型半胱氨酸血症，Hcy（0.03 μmol/g 体重）从第 30 天到第 60 天皮下给药。对照组大鼠给予相同体积的生理盐水。结果表明，Hcy 显著降低了突触小体部分的核苷酸水解，并增加了大鼠大脑皮质中 E-NTPDase1 和外切 5'-核苷酸酶的转录本。Hcy 处理大鼠 CSF 中的 ATP 水平显著升高，而 Ado 水平降低。这些发现表明，ATP 和 Ado 水平的失衡可能部分参与了轻度高同型半胱氨酸血症的脑毒性。
