Striatal dopamine output is compromised within +/- BDNF mice
Striatal dopamine output is compromised within +/- BDNF mice
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DOI：
10.1002/syn.10027
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发表时间：
2002-02-01
期刊：
影响因子：
2.3
通讯作者：
Walro, JM
中科院分区：
文献类型：
--
作者：
Dluzen, DE;Anderson, LI;Walro, JM
我们以前报道，小鼠缺乏一个脑源性神经营养因子（BDNF）等位基因表现出纹状体多巴胺（DA）浓度升高，但受损的行为反应，涉及黑质纹状体多巴胺（NSDA）系统。为了验证这一假设，这些纹状体DA浓度升高与干扰NSDA功能，我们比较了杂合突变（+/-）和野生型同窝对照（+/+）BDNF小鼠的条件下，一个完整的NSDA系统，以及以下甲基苯丙胺（MA）诱导的神经毒性纹状体DA输出。从灌流CS组织碎片的基础DA输出在+/+和+/- BDNF小鼠之间没有差异。钾离子（K+）刺激的+/+小鼠完整纹状体碎片的DA输出显著大于+/- BDNF小鼠。MA处理后，+/+小鼠的K+刺激DA输出在统计学上等同于+/- BDNF小鼠。相对于+/+小鼠，完整小鼠和MA处理小鼠中+/- BDNF小鼠的纹状体DA浓度均升高，尽管并不显着。MA治疗后，两种基因型的纹状体DA浓度均显著降低;然而，+/+小鼠的DA耗竭程度显著更高。综合分析，这些数据显示了BDNF突变对纹状体DA浓度和输出的不同影响。值得注意的是，+/+与+/- BDNF小鼠的纹状体DA浓度较低，这与前者的K+刺激DA输出显著增加形成对比。这种差异在MA治疗后消失。这些结果表明，在+/- BDNF突变小鼠中，NSDA系统内DA释放动力学过程可能受到损害。(C)2001 Wiley-Liss，Inc.
We reported previously that mice lacking one brain-derived neurotrophic factor (BDNF) allele demonstrate elevated striatal dopamine (DA) concentrations but impaired behavioral responses involving the nigrostriatal dopaminergic (NSDA) system. To test the hypothesis that these elevated striatal DA concentrations are associated with perturbed NSDA functioning, we compared striatal DA output between heterozygous mutant (+/-) and wild-type littermate control (+/+) BDNF mice under conditions of an intact NSDA system, as well as following methamphetamine (MA)induced neurotoxicity. Basal DA output from superfused CS tissue fragments did not differ between +/+ and +/- BDNF mice. Potassium (K+) stimulated DA outputs from intact striatal fragments of +/+ mice were significantly greater than that of +/- BDNF mice. Following MA treatment, K+ stimulated DA output of +/+ mice was statistically equivalent to +/- BDNF mice. Striatal DA concentrations of +/- BDNF mice were elevated, albeit not significantly, in both intact and MA-treated mice relative to +/+ mice. Following MA treatment, striatal DA concentrations were significantly decreased for both genotypes; however, the degree of DA depletion was significantly greater in +/+ mice. Analyzed collectively, these data show the differential effects exerted by a BDNF mutation upon striatal DA concentrations and output. Notably, lower striatal DA concentrations of +/+ vs. +/- BDNF mice can be contrasted with the significantly greater K+ stimulated DA output from the former. This difference was abolished following MA treatment. These results suggest that processes involved with the dynamics of DA release within the NSDA system may be compromised in +/- BDNF mutant mice. (C) 2001 Wiley-Liss, Inc.