Parvalbumin-positive GABAergic interneurons deficit in the hippocampus in Gunn rats: A possible hyperbilirubinemia-induced animal model of schizophrenia
Parvalbumin-positive GABAergic interneurons deficit in the hippocampus in Gunn rats: A possible hyperbilirubinemia-induced animal model of schizophrenia
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DOI：
10.1016/j.heliyon.2019.e02037
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发表时间：
2019-07-01
期刊：
影响因子：
4
通讯作者：
Inagaki, Masatoshi
中科院分区：
文献类型：
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作者：
Hayashida, Maiko;Miyaoka, Tsuyoshi;Inagaki, Masatoshi
死后组织中GABA能标记物的减少在精神分裂症中被一致地发现。重要的是，GABA能神经元中的这些改变不是全局性的，这意味着它们在中间神经元的不同亚类中更普遍，包括表达钙结合蛋白小清蛋白的那些。海马中小清蛋白表达的减少不仅在死后的人类精神分裂症患者中是一致的观察，而且在多种啮齿动物疾病模型中也是一致的观察。我们曾报道过Wistar品系的一种突变型先天性高胆红素血症模型大鼠（古恩大鼠）表现出与几种精神分裂症啮齿动物模型相似的行为异常，如过度运动活动、前脉冲抑制缺陷、不适当的社会交往、识别记忆受损。几项动物研究将palvalbumin的重要性与海马异常活动和精神分裂症样行为联系起来，在此，我们发现，与Wistar对照大鼠相比，古恩大鼠（先天性高胆红素血症模型大鼠）的CA1、CA3和总海马中的palvalbumin阳性细胞密度显著降低。检测血清UCB水平与海马PV表达缺失的相关性。海马中PV表达的减少可能提示与古恩大鼠的精神分裂样行为的行为异常相关联，与Wistar对照大鼠相比。
A reduction of GABAergic markers in postmortem tissue is consistently found in schizophrenia. Importantly, these alterations in GABAergic neurons are not global, which means they are more prevalent among distinct subclasses of interneurons, including those that express the calcium binding protein parvalbumin.A decreased expression of parvalbumin in the hippocampus is a consistent observation not only in postmortem human schizophrenia patients, but also in a diverse number of rodent models of the disease.Meanwhile, previously we reported that the congenital hyperbilirubinemia model rats (Gunn rats), which is a mutant of the Wistar strain, showed behavioral abnormalities, for instance, hyperlocomotor activity, deficits of prepulse inhibition, inappropriate social interaction, impaired recognition memory similar with several rodent models of schizophrenia. Several animal studies linked the importance of palvalbumin in relation to abnormal hippocampal activity and schizophrenia-like behavior.Here, we show that parvalbumin positive cell density was significantly lower in the CA1, CA3 and the total hippocampus of Gunn rats (congenital hyperbilirubinemia model rats) compared to Wistar control rats. The correlations between serum UCB levels and loss of PV expression in the hippocampus were also detected. The decreases in the PV-expression in the hippocampus might suggest an association of the behavioral abnormalities as schizophrenia-like behaviors of Gunn rats, compared to the Wistar control rats.