摘要
精神疾病的人类基因数据反复证明了神经发育和神经形成与多种基因的参与相关。神经形成是一个生物过程,是大脑发育的关键,贯穿一生。神经形成是一个多步骤的过程从神经干细胞/祖细胞的分裂开始,同时导致定向分化细胞包括神经元和神经胶质细胞的生产和自我更新。在神经形成过程中的一些小缺陷,如产生更少的新神经元和神经回路的畸形,能代表精神疾病在动物模型中分子和细胞水平的表型(这里称为“微表型”)。然而,微表型不易用作生物标记。我们关注在生理条件下,感觉运动控制缺陷,可通过前脉冲抑制(PPI)测试来评分。受损的PPI被认为是一些精神疾病如:精神分裂症、自闭症和其他神经发育障碍,的一个引人注目的表型(生物标记物)。因为PPI的神经回路涉及海马 — 一个独特的大脑区域,出生后神经形成之处。我们假设青春期前期的神经形成障碍对感知运动控制缺陷的发生至关重要。为了检测这一假说,我们研究了一个能影响PPI的神经形成的关键时期。在这一范例中,我们引入了一个丰富的环境来恢复神经形成,从而恢复小鼠的PPI缺陷。我们提到海马齿状回(DG)中新生神经元的成熟障碍和海马中γ-氨基丁酸能神经元的损伤,这可能被视为与PPI缺陷有关的微表型。更精确地基因控制神经形成的模型(精确的时间点或周期)需要进一步的调查研究来支持我们的假设。
关键词: γ-氨基丁酸能神经元,神经形成,前脉冲抑制,感知运动控制
Current Molecular Medicine
Title:Neurogenesis and Sensorimotor Gating: Bridging a Microphenotype and an Endophenotype
Volume: 15 Issue: 2
Author(s): N. Osumi, N. Guo, M. Matsumata and K. Yoshizaki
Affiliation:
关键词: γ-氨基丁酸能神经元,神经形成,前脉冲抑制,感知运动控制
摘要: Human genetic data on psychiatric disorders repeatedly demonstrate the involvement of various genes that are associated with neural development and neurogenesis. Neurogenesis is a biological process that is critical in brain development and continues throughout life. Neurogenesis is a multi-step process starting from the division of neural stem cells/progenitor cells, leading to self-renewal and simultaneously to the production of lineage-committed cells, including neurons and glial cells. Minor defects in the neurogenesis process, such as production of fewer new neurons and malformation of neural circuits, could represent phenotypes of psychiatric disorders at molecular and cellular levels in animal models (here termed as “microphenotypes”). However, microphenotypes are not easily used as biomarkers. We have focused on a physiological condition, sensorimotor gating deficits, that can be scored by a prepulse inhibition (PPI) test. Impaired PPI is considered to be one of the compelling endophenotypes (biological markers) of mental disorders such as schizophrenia, autism, and other neurodevelopmental disorders. Because the neural circuit for PPI involves the hippocampus, a unique brain region where neurogenesis occurs postnatally, we hypothesize that an impairment of preadolescent neurogenesis is critical for the onset of sensorimotor gating defects. To test this hypothesis, we investigated a critical period of neurogenesis that can affect PPI. In this paradigm, we introduced an enriched environment to restore neurogenesis, thereby recovering PPI deficits in mice. We noted impairments in the maturation of newborn neurons in the hippocampal dentate gyrus (DG) and GABAergic neurons in the hippocampus, which could be considered as microphenotypes associated with PPI defects. More precise genetically controlled neurogenesis models (with precise time points or periods) are needed to be studied in further investigation to support our hypothesis.
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Cite this article as:
N. Osumi, N. Guo, M. Matsumata and K. Yoshizaki , Neurogenesis and Sensorimotor Gating: Bridging a Microphenotype and an Endophenotype, Current Molecular Medicine 2015; 15 (2) . https://dx.doi.org/10.2174/1566524015666150303002834
DOI https://dx.doi.org/10.2174/1566524015666150303002834 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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