Bumetanide Prevents Brain Trauma-Induced Depressive-Like Behavior
Bumetanide Prevents Brain Trauma-Induced Depressive-Like Behavior
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DOI：
10.3389/fnmol.2019.00012
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发表时间：
2019-02-05
影响因子：
4.8
通讯作者：
Pellegrino, Christophe
中科院分区：
文献类型：
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作者：
Goubert, Emmanuelle;Altvater, Marc;Pellegrino, Christophe
脑创伤触发一系列有害事件，导致耐药性癫痫、抑郁和认知功能障碍的发生率增加。导致这些改变的潜在机制知之甚少，并且没有减弱这些后遗症的治疗。使用受控皮质撞击作为成年小鼠脑创伤的实验模型，我们发现钠-钾-氯化物输入者（NKCC 1）特异性拮抗剂布美他尼对抑郁样行为的出现具有强烈的抑制作用。我们证明，这种行为的改变与海马齿状回内创伤后继发性神经发生的损伤有关。介导布美他尼作用的机制涉及脑创伤后氯调节蛋白表达的早期瞬时变化和GABA（A）介导的从超极化到去极化的传递的定性变化。这项工作为人类创伤后抑郁症的早期治疗开辟了新的视角。我们的研究结果强烈表明，布美他尼可能构成一个有效的预防性治疗，以减少脑外伤的神经和精神后果。
Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression, and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels are not available. Using controlled-cortical impact as an experimental model of brain trauma in adult mice, we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on the appearance of depressive-like behavior. We demonstrate that this alteration in behavior is associated with an impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in the expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission from hyperpolarizing to depolarizing after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.