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首页> 外文期刊>Cellular Physiology and Biochemistry >Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala
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Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala

机译：磷脂酰肌醇依赖性激酶缺乏症增加杏仁核的焦虑感并降低GABA和5-羟色胺的含量

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摘要

Pathological anxiety is paralleled by deficits in serotonergic and GABAergic neurotransmission in the amygdala. Conversely, anxiety disorders and depression may be reversed by brain-derived neurotrophic factor ( BDNF). BDNF signaling involves Phosphatidylinositol 3-Kinase / 3-phosphoinositide-dependent protein kinase 1 (PI3K/PDK1). We thus hypothesized that impaired function of PDK1 might be associated with increased anxiety and concomitant neurotransmitter changes. Here we used the hypomorphic PDK1(hm) mouse to investigate anxiety behavior in different settings: PDK1(hm) mice differed from Wt littermates PDK1(WT) in several behavioral measures related to anxiety and exploration, namely in the open field, dark-light box, O-maze and startle response. Further we analyzed the brain substrate underlying this phenotype and found significantly decreased GABA, taurine and serotonin concentrations in the amygdala and olfactory bulb of PDK1(hm) mice, while BDNF and nerve growth factor (NGF) concentrations were not significantly different between PDK1(hm) and PDK1(WT) mice. These results suggest that impaired PI3K signaling in the PDK1(hm) mouse reduces concentrations of GABA and serotonin in anxiety related brain regions and can serve as a molecular substrate for behavior indicative for anxious and depressive-like mood states.
机译：病理性焦虑伴随着杏仁核中血清素和GABA能神经传递的缺陷。相反，焦虑障碍和抑郁症可以通过脑源性神经营养因子（BDNF）逆转。 BDNF信号传导涉及磷脂酰肌醇3-激酶/ 3-磷酸肌醇依赖性蛋白激酶1（PI3K / PDK1）。因此，我们假设PDK1的功能受损可能与焦虑增加和神经递质变化同时发生有关。在这里，我们使用亚变形的PDK1（hm）小鼠研究了不同环境下的焦虑行为：PDK1（hm）小鼠与Wt同窝仔PDK1（WT）在与焦虑和探索有关的几种行为指标上有所不同，即在旷野，暗光下框，O型迷宫和惊吓反应。进一步，我们分析了该表型的潜在脑底物，发现PDK1（hm）小鼠的杏仁核和嗅球中的GABA，牛磺酸和5-羟色胺浓度显着降低，而PDK1（hm）的BDNF和神经生长因子（NGF）浓度无显着差异）和PDK1（WT）小鼠。这些结果表明，PDK1（hm）小鼠中PI3K信号传导的减弱会降低与焦虑相关的大脑区域中GABA和5-羟色胺的浓度，并可作为指示焦虑和抑郁样情绪状态的行为的分子底物。

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