Excitatory and inhibitory synaptic dysfunction in mania: an emerging hypothesis from animal model studies.
Excitatory and inhibitory synaptic dysfunction in mania: an emerging hypothesis from animal model studies.
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DOI：
10.1038/s12276-018-0028-y
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发表时间：
2018-04-09
影响因子：
12.8
通讯作者：
Han K
中科院分区：
文献类型：
--
作者：
Lee Y;Zhang Y;Kim S;Han K
双相情感障碍（BD）是一种常见的精神疾病，其特征是在抑郁和躁狂之间反复出现情绪波动，并且与高昂的治疗费用相关。躁狂发作的存在是BD的定义特征，在此期间，患者经历活动，能量和情绪的极度升高，睡眠模式的变化严重损害了他们在日常生活中的功能。尽管在概括人类疾病的复杂特征方面存在一些局限性，但已经产生并表征了几种躁狂症的啮齿动物模型，这为理解其潜在的致病机制提供了重要的见解。在这些机制中，包括额叶皮质、海马和纹状体在内的一些脑区的神经元兴奋性和抑制性（E/I）突触功能障碍是解释躁狂症的一个新兴假说。在这篇综述中，我们强调了最近的研究啮齿动物躁狂模型有损害的E/I突触的发展和功能。我们还总结了一些情绪稳定剂对E/I突触的分子和功能变化，这些变化可能有助于药物的治疗效果。此外，我们还讨论了这一新兴假设研究的潜在未来方向，以更好地将基础研究的结果与这种毁灭性精神疾病患者的治疗联系起来。对啮齿动物的研究提供了对双相情感障碍的深入了解，这可能有助于理解和治疗这种常见的和使人衰弱的疾病。首尔高丽大学的Kihoon Han和他的同事们回顾了用小鼠和大鼠模拟双相情感障碍患者躁狂发作的研究。这项研究支持了一个新兴的假设，即躁狂发作时大脑中神经传递的特定问题。这一假说表明，可能涉及到特定神经细胞之间的信号传递，这些神经细胞的正常功能是兴奋或抑制其他神经细胞。它还表明大脑中与躁狂发作最相关的区域。在受影响的神经连接-所谓的突触-由情绪稳定药物带来的变化进行了检查。这一假设为研究人员探索治疗方案提供了新的方法。
Bipolar disorder (BD) is a common psychiatric disorder characterized by recurrent mood swings between depression and mania, and is associated with high treatment costs. The existence of manic episodes is the defining feature of BD, during which period, patients experience extreme elevation in activity, energy, and mood, with changes in sleep patterns that together severely impair their ability to function in daily life. Despite some limitations in recapitulating the complex features of human disease, several rodent models of mania have been generated and characterized, which have provided important insights toward understanding its underlying pathogenic mechanisms. Among the mechanisms, neuronal excitatory and inhibitory (E/I) synaptic dysfunction in some brain regions, including the frontal cortex, hippocampus, and striatum, is an emerging hypothesis explaining mania. In this review, we highlight recent studies of rodent manic models having impairments in the E/I synaptic development and function. We also summarize the molecular and functional changes of E/I synapses by some mood stabilizers that may contribute to the therapeutic efficacy of drugs. Furthermore, we discuss potential future directions in the study of this emerging hypothesis to better connect the outcomes of basic research to the treatment of patients with this devastating mental illness. Studies in rodents offer insights into bipolar disorder that may help understanding and treatment of this common and debilitating condition. Kihoon Han and colleagues at Korea University in Seoul review research using mice and rats to model the episodes of mania in patients with bipolar disorder. The research supports an emerging hypothesis implicating specific problems with nervous transmission in the brain in the onset of mania. The hypothesis suggests that the transmission of signals between particular nerve cells whose normal function is either to excite or to inhibit other nerve cells may be involved. It also indicates regions of the brain most involved in manic episodes. Changes at the affected nerve junctions—called synapses—brought about by mood-stabilizing drugs are examined. The hypothesis suggests new approaches to treatment options for researchers to explore.