Chronic mild stress impairs latent inhibition and induces region-specific neural activation in CHL1-deficient mice, a mouse model of schizophrenia.
Chronic mild stress impairs latent inhibition and induces region-specific neural activation in CHL1-deficient mice, a mouse model of schizophrenia.
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DOI：
10.1016/j.bbr.2017.06.033
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发表时间：
2017-08-30
影响因子：
2.7
通讯作者：
Buhusi CV
中科院分区：
文献类型：
--
作者：
Buhusi M;Obray D;Guercio B;Bartlett MJ;Buhusi CV
精神分裂症是一种以信息处理异常和注意力缺陷为特征的神经发育障碍。精神分裂症有很高的遗传成分，但由环境因素促成，正如精神分裂症的“两次打击”理论所提出的那样。在这里，我们比较了潜伏抑制作为学习和注意力的一种衡量标准，在CHL 1缺陷小鼠，精神分裂症的动物模型，和他们的野生型同窝出生，在无压力和慢性轻度压力条件下。所有未应激的小鼠以及应激的野生型小鼠均表现出潜伏性抑制。相比之下，CHL 1缺陷小鼠在暴露于慢性应激后没有表现出潜在的抑制。神经元激活（c-Fos阳性细胞计数）的差异，注意到在大脑区域与潜在的抑制：神经元激活的前边缘/边缘下皮质和核壳的压力只受影响。基底外侧杏仁核和腹侧海马的神经元激活受到压力和基因型的独立影响。最重要的是，神经激活的丘脑核的核心受到压力和基因型之间的交互作用。这些结果提供了强有力的支持的“两击”（基因x环境）的影响，在CHL 1缺陷型小鼠的潜伏抑制，并确定CHL 1缺陷型小鼠精神分裂症样学习和注意力障碍的模型。
Schizophrenia is a neurodevelopmental disorder characterized by abnormal processing of information and attentional deficits. Schizophrenia has a high genetic component but is precipitated by environmental factors, as proposed by the ‘two-hit’ theory of schizophrenia. Here we compared latent inhibition as a measure of learning and attention, in CHL1-deficient mice, an animal model of schizophrenia, and their wild-type littermates, under no-stress and chronic mild stress conditions. All unstressed mice as well as the stressed wild-type mice showed latent inhibition. In contrast, CHL1-deficient mice did not show latent inhibition after exposure to chronic stress. Differences in neuronal activation (c-Fos-positive cell counts) were noted in brain regions associated with latent inhibition: Neuronal activation in the prelimbic/infralimbic cortices and the nucleus accumbens shell was affected solely by stress. Neuronal activation in basolateral amygdala and ventral hippocampus was affected independently by stress and genotype. Most importantly, neural activation in nucleus accumbens core was affected by the interaction between stress and genotype. These results provide strong support for a ‘two-hit’ (genes x environment) effect on latent inhibition in CHL1-deficient mice, and identify CHL1-deficient mice as a model of schizophrenia-like learning and attention impairments.
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