Traficante Anna, Riozzi Barbara, Cannella Milena, Rampello Liborio, Squitieri Ferdinando, Battaglia Giuseppe
Department of Neuroscience, Istituto Neurologico Mediterraneo Neuromed, Località Camerelle, Pozzilli, Italy.
Neuroreport. 2007 Dec 3;18(18):1997-2000. doi: 10.1097/WNR.0b013e3282f262ca.
We have used the R6/2 mice to study cortico-striatal glutamatergic transmission by microdialysis in freely moving mice. Basal extracellular striatal glutamate concentrations were lower in R6/2 mice at 12 weeks of age, but not at 6 weeks of age, when neurological symptoms start to develop. In contrast, K-induced glutamate release was blunted in the striatum of R6/2 mice at both 6 and 12 weeks of age as compared with age-matched controls. We also found a substantial reduction in striatal pro-BDNF (brain derived neurotrophic factor) levels associated with no changes in the mature form of BDNF, as assessed by immunoblotting, in 12-week-old R6/2 mice, suggesting a reduced turnover rate of BDNF in the striatum of these mice. These data support the hypothesis of a cortico-striatal dysfunction in Huntington's disease.
我们使用R6/2小鼠，通过在自由活动的小鼠中进行微透析来研究皮质-纹状体谷氨酸能传递。12周龄的R6/2小鼠纹状体细胞外谷氨酸基础浓度较低，但在6周龄时（此时神经症状开始出现）并非如此。相比之下，与年龄匹配的对照组相比，6周龄和12周龄的R6/2小鼠纹状体中K诱导的谷氨酸释放均减弱。我们还发现，通过免疫印迹评估，12周龄的R%/2小鼠纹状体中前体脑源性神经营养因子（pro-BDNF）水平大幅降低，而成熟形式的BDNF没有变化，这表明这些小鼠纹状体中BDNF的周转率降低。这些数据支持亨廷顿病中皮质-纹状体功能障碍的假说。
