双相障碍离子调节改变的动物模型综述。
Review of animal models of bipolar disorder that alter ion regulation.
机构信息
University of Louisville School of Medicine, Department of Psychiatry and Behavioral Medicine, Louisville, KY, USA.
University of Louisville School of Medicine, Department of Psychiatry and Behavioral Medicine, Louisville, KY, USA.
出版信息
Neurosci Biobehav Rev. 2019 Dec;107:208-214. doi: 10.1016/j.neubiorev.2019.09.016. Epub 2019 Sep 12.
BACKGROUND
Accurate modeling of psychiatric disorders in animals is essential for advancement in our understanding and treatment of the severe mental illnesses. Of the multiple models available for bipolar illness, the ones that disrupt ion flux are currently the only ones that meet the three criteria for validity: face validity, construct validity, and predictive validity.
METHODS
A directed review was performed to evaluate animal models for mania in which ion dysregulation was the key intervention.
RESULTS
Three models are identified. All focus on disruption of the sodium potassium pump. One is pharmacologic and requires surgical insertion of an intracerebroventricular (ICV) cannula and subsequent administration of ouabain. Two are genetic and are based on heterozygote knockout (KO) of the alpha2 or alpha3 subunits of the sodium pump. Alpha2 KOs are believed to have altered glial function, and they do not appear to have a full array of manic symptoms. Alpha3 KOs appear to be the best characterized animal model for bipolar disorder currently available.
CONCLUSION
Animal models that disrupt ion regulation are more inclined to model both mania and depression; and are thus the most promising models available. However, other models are important for demonstrating mechanisms in important pathophysiologic aspect of bipolar disorder.
背景
在动物中准确模拟精神疾病对于我们深入理解和治疗严重精神疾病至关重要。在多种双相情感障碍模型中，目前只有那些干扰离子流的模型符合有效性的三个标准：表面效度、结构效度和预测效度。
方法
进行了定向综述，以评估以离子失调为关键干预措施的躁狂症动物模型。
结果
确定了三种模型。所有模型都侧重于破坏钠钾泵。一种是药理学模型，需要进行脑室内（ICV）套管的外科插入，然后给予哇巴因。两种是遗传学模型，基于钠泵的 alpha2 或 alpha3 亚单位的杂合子敲除（KO）。alpha2 KO 被认为改变了神经胶质功能，并且它们似乎没有完全的躁狂症状。alpha3 KO 似乎是目前可用的最具特征的双相情感障碍动物模型。
结论
干扰离子调节的动物模型更倾向于模拟躁狂和抑郁；因此是最有前途的模型。然而，其他模型对于证明双相情感障碍重要病理生理方面的机制很重要。
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