脂多糖激活所致大鼠抑郁样行为及对海马神经细胞钾电流变化的影响

Upregulation of K+ Current in Hippocampal Neurons from Rat with Depressive-Like Behavior Induced by Lipopolysaccharide

采用细胞因子刺激剂脂多糖(lipopolysaccharide,LPS)为免疫激活手段,研究LPS诱导的免疫激活产生的抑郁样行为及对海马神经细胞电压依赖钾电流变化的影响。应用膜片钳技术对海马神经细胞钾电流进行全细胞记录,比较抑郁样行为大鼠与正常大鼠钾离子通道电流密度和激活特性的变化。结果发现,与生理盐水对照组相比,一次LPS注射后2hr,实验组动物产生抑郁样行为,同时急性观察的海马神经细胞的钾离子通道的电流密度呈现显著升高(p<0.01);而一次LPS注射后24hr,动物的抑郁样行为消失,且急性观察的海马神经细胞的钾离子通道与对照组相比较,其电流密度和激活曲线没有显著性变化。结论:LPS诱导的抑郁样行为,与LPS诱导的海马神经细胞电压依赖钾电流的上调在时程上同步,提示钾离子通道可能参与免疫激活所致的抑郁样行为。

Lipopolysaccharide （LPS）-induced immunity activation can result in evident depressive-like behavior, such as anhedonia and reduced locomotion. Earlier studies have shown that K＋ channels, such as Kv7 and TREK-1, are involved in the development of depressive-like behavior in animal models. In the present study, we show that LPS （200 μg/kg） could induce significant short-term depressive-like behavior in rat. In order to get insight into the underlying molecular mechanism, we investigated the potential involvement of rat hippocampal neuron voltage-dependent K＋ channels in the depressive-like behaviors induced by LPS. Methods： Twenty rats were randomly divided into LPS and control groups, each with ten rats. The rats in the LPS group were injected with LPS （200 ~tg/kg）, while saline was injected in the rats of the control group. The saccharin preference test and open field test were carried out 2 hours and 24 hours after injection of LPS to assess short-term or long-term effects on animal behavior, respectively. Next, 12 rats were randomly divided into LPS 2 hr, LPS 24 hr and control groups, each with four rats for assessing the effect of LPS on K＋ channel currents of hippocampal neurons by using whole-cell patch-clamp configuration. Results： The data showed that LPS induced depressive-like behavior in rat after 2 hours of single injection. However, this depressive-like behavior was recovered after 24 hours of single LPS injection. In agreement with these behavioral observations, voltage-dependent K＋ current density was increased in neurons isolated from rat after 2 hours of single LPS injection, whereas no significant change was found after 24 hours injection. Conclusion： Our results demonstrate that LPS-induced immunity activation can result in evident short term depressive-like behavior in rats, which are coincident with LPS induced up-regulation of voltage-dependent K＋ current in rat hippocampal neurons. This result suggests that voltage-dependent K＋ current might contribute to the development of the depressive-like behavior induced by LPS.