具有未成熟齿状回表型的神经精神疾病小鼠模型的远程空间记忆缺陷。

IF 3.7 2区 医学 Q1 CLINICAL NEUROLOGY
Hirotaka Shoji, Hideo Hagihara, Isabella A Graef, Gerald R Crabtree, Freesia L Huang, Paul W Frankland, Tsuyoshi Miyakawa
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引用次数: 0

摘要

背景:海马齿状回(DG)是影响近期记忆和远期记忆的重要区域。该区域内的颗粒细胞发生成人神经发生,在成年期通过遗传和环境因素经历动态和可逆的成熟。DG颗粒细胞的伪未成熟状态,称为未成熟DG (iDG),已在某些突变株的成年小鼠中观察到,这些突变株被认为是神经精神和神经退行性疾病(如智力残疾、精神分裂症、自闭症和阿尔茨海默病)的动物模型。然而,在小鼠模型中,iDG表型与近期和远程记忆之间的关系尚不清楚。方法:我们在5种iDG表型疾病的突变小鼠模型中,包括Camk2a杂合敲除(HET KO)、前脑特异性钙调磷酸酶条件型KO (cKO)、Neurogranin KO、Hivep2 (Schnurri-2) KO和hap - j20转基因小鼠,在巴恩斯圆迷宫任务中评估空间记忆。结果:Camk2a HET KO小鼠和J20小鼠在最后一次训练后1天和4周的记忆保持测试中,在目标周围停留的时间比野生型对照小鼠要短。钙调磷酸酶cKO、神经粒蛋白KO和Schnurri-2 KO小鼠在训练后1天的保留测试中,在目标周围停留的时间与野生型小鼠没有显著差异,但在4周后的重新测试中,这些突变体在目标周围停留的时间比野生型小鼠少。结论:这些结果表明,显示iDG表型的神经精神和神经退行性疾病小鼠模型显示出远程空间记忆缺陷的共同行为特征,提示DG颗粒细胞的伪未成熟状态可能参与远程记忆功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Remote spatial memory deficits in mouse models of neuropsychiatric disorders with immature dentate gyrus phenotype.

Background: The hippocampal dentate gyrus (DG) is a critical region that contributes to recent and remote memory. Granule cells within this region, in which adult neurogenesis occurs, undergo dynamic and reversible maturation via genetic and environmental factors during adulthood. A pseudo-immature state of DG granule cells, called immature DG (iDG), has been observed in the adult mice of certain mutant strains, which are considered animal models of neuropsychiatric and neurodegenerative disorders, such as intellectual disability, schizophrenia, autism, and Alzheimer's disease. However, the association between the iDG phenotype and recent and remote memories in the mouse models remains unclear.

Methods: We assessed spatial memory in the Barnes circular maze task in five mutant mouse models of the disorders with the iDG phenotype, including Camk2a heterozygous knockout (HET KO), forebrain-specific Calcineurin conditional KO (cKO), Neurogranin KO, and Hivep2 (Schnurri-2) KO, and hAPP-J20 transgenic mice.

Results: Camk2a HET KO mice and J20 mice spent less time around the target than their wild-type control mice in the memory retention tests one day and four weeks after the last training session. Calcineurin cKO, Neurogranin KO, and Schnurri-2 KO mice showed no significant differences in the time spent around the target from wild-type mice in the retention test 1 day after the training session, but those mutants spent less time around the target than their wild-type mice in the retest conducted four weeks later.

Conclusions: These results indicated that mouse models of neuropsychiatric and neurodegenerative disorders exhibiting the iDG phenotype demonstrate a common behavioral characteristic of remote spatial memory deficits, suggesting the potential involvement of the pseudo-immature state of DG granule cells in remote memory dysfunction.

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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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