Upregulations of α1 adrenergic receptors and noradrenaline synthases in the medial prefrontal cortex are associated with emotional and cognitive dysregulation induced by post-weaning social isolation in male rats

Upregulations of α1 adrenergic receptors and noradrenaline synthases in the medial prefrontal cortex are associated with emotional and cognitive dysregulation induced by post-weaning social isolation in male rats
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内侧前额叶皮层α1肾上腺素受体和去甲肾上腺素合酶的上调与雄性大鼠断奶后社会隔离引起的情绪和认知失调有关

DOI:
10.1016/j.neulet.2023.137071
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发表时间:
2023
影响因子:
2.5
通讯作者:
Enjoji Munechika
Enjoji Munechika
中科院分区:
医学4区
文献类型:
--
作者:
Kawanabe Shunsuke;Mori Masayoshi;Harada Hiroyoshi;Murata Yusuke;Ohe Kenji;Enjoji Munechika

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早期的社会隔离会导致情绪和认知失调,例如增加攻击性和焦虑,并降低内侧前额叶皮层(mPFC)的神经元兴奋性。mPFC中的去甲肾上腺素能系统通过α 1或α 2A肾上腺素能受体调节情绪和认知功能,这取决于去甲肾上腺素水平。然而,社会隔离引起的mPFC去甲肾上腺素能系统的变化还没有报道。在这里,雄性Wistar大鼠接受连续9周的断奶后社会隔离,并进行行为测试(新物体识别,高架十字迷宫,攻击性,强迫游泳,顺序)。通过蛋白质印迹法检测mPFC去甲肾上腺素能系统(α 1和α 2 A肾上腺素能受体、酪氨酸羟化酶和多巴胺-β-羟化酶用作去甲肾上腺素合成和释放的指标)中的蛋白质表达水平。社会隔离导致认知功能障碍,焦虑样行为和攻击性,但不是行为绝望。社会隔离大鼠mPFC中α 1肾上腺素能受体、酪氨酸羟化酶和多巴胺-β-羟化酶的蛋白水平升高;两组间α 2A肾上腺素能受体表达水平无显著差异。高浓度去甲肾上腺素引起的mPFC α 1肾上腺素能受体的优先激活可能参与了社交孤立诱导的情绪和认知调节障碍。靶向α 1肾上腺素能受体信号通路是治疗具有情绪和认知失调等症状特征的精神疾病的潜在治疗策略。
Early-life social isolation induces emotional and cognitive dysregulation, such as increased aggression and anxiety, and decreases neuron excitability in the medial prefrontal cortex (mPFC). The noradrenergic system in the mPFC regulates emotion and cognitive function via α1or α2Aadrenergic receptors, depending on noradrenaline levels. However, social isolation-induced changes in the mPFC noradrenergic system have not been reported. Here, male Wistar rats received post-weaning social isolation for nine consecutive weeks and were administered behavioral tests (novel object recognition, elevated plus maze, aggression, and forced swimming, sequentially). Protein expression levels in the mPFC noradrenergic system (α1and α2Aadrenergic receptors, tyrosine hydroxylase, and dopamine-β-hydroxylase used as indices of noradrenaline synthesis and release) were examined through western blotting. Social isolation caused cognitive dysfunction, anxiety-like behavior, and aggression, but not behavioral despair. Socially-isolated rats exhibited increased protein levels of the α1adrenergic receptor, tyrosine hydroxylase, and dopamine-β-hydroxylase in the mPFC; there was no significant difference between the groups in the α2Aadrenergic receptor expression levels. Preferential activation of the α1adrenergic receptor caused by high noradrenaline concentration in the mPFC may be involved in social isolation-induced emotional and cognitive regulation impairments. Targeting the α1adrenergic receptor signaling pathway is a potential therapeutic strategy for psychiatric disorders with symptomatic features such as emotional and cognitive dysregulation.
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