Neurochemical mechanism for the behavioral disturbances in the Se-deficient mice : an evaluation with in vivo microdialysis.

我们以前曾报道过，小鼠长期硒缺乏会导致行为改变。阐明硒缺乏对行为影响的潜在神经化学机制是本研究的目标。建立小鼠断奶后硒缺乏模型；在此过程中，我们发现Se浓度在大脑中的下降明显大于小脑和脑干。考虑到这一结果以及之前的研究结果，我们检测了硒缺乏小鼠体内微透析纹状体中多巴胺（DA）的细胞外浓度（作为释放指标）。选择体内微透析来评估硒缺乏可能的神经化学效应，因为它与行为输出有直接联系。aporox之后。在低硒饮食4周后，在“基础”条件下或在高k ^+灌注的去极化刺激下，缺硒组与对照组（足硒组）的细胞外DA浓度没有差异。缺硒12周后，缺硒组在高k ^+灌注时DA增加，明显大于对照组。为了确定DA代谢的这种改变是否与硒缺乏的任何行为影响有关，进行了加或不加nomifenine (NOM)（一种DA转运体的选择性抑制剂）的露天试验。缺硒14周后，缺硒组裸地装置的活性显著高于对照组。先前给予NOM增加了两组的活性，在缺乏组中效果略微夸大。此外，这一剂量的NOM增加了纹状体的细胞外DA。综上所述，这些结果表明硒缺乏通过增强纹状体中DA的释放而增加了裸地活性。

We have previously reported that a prolonged Se deficiency in mice results in behavioral alteration. Elucidation of the underlying neurochemical mechanism for this behavioral effect of Se deficiency was the goal of the present study.A model for postweaning Se deficiency was developed using mice ; in this process, we have found that decrease in Se concentration was significantly more pronounced in cerebrum than in cerebellum or in brain stem. Taking this result as well as the results from preceding studies into account, we have examined the extracellular concentration (as an index of release) of dopamine (DA) in the striatum of Se-deficient mice with in vivo microdialysis. In vivo microdialysis was selected to evaluate possible neurochemical effect (s) of Se deficiency because of its direct link to behavioral output. After aporox.4 weeks on low-Se-diet regimen, the Se-deficient group was not different from the control (Se-adequate) group regarding the extracellular concentration of DA under a "basal" condition or under a depolarizing stimulus with high-K^+ perfusion. After 12 week of Se deficiency, the deficient group showed a DA increase upon high-K^+ perfusion, which was significantly greater than the one observed in the control group. To determine whether this alteration in the DA metabolism is related with any behavioral effects of Se deficiency, an open-field test with or without nomifensine (NOM), a selective inhibitor for the DA transporter, was conducted. After 14 week of Se deficiency, the activity in the open-field apparatus was significantly greater in the Se-deficient group than in the control group. Prior administration of NOM increased the activity of both the groups, the effect being slightly exaggerated in the deficient group. In addition, this dose of NOM increased extracellular DA in the striatum. Taken together, these results suggested that the Se deficiency increased the open-field activity by an enhanced DA release in the striatum.