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敲低候选阅读障碍易感性基因同源物 dyx1c1 在啮齿动物中的表达:对听觉处理、视觉注意以及皮质和丘脑解剖结构的影响。

Knockdown of the candidate dyslexia susceptibility gene homolog dyx1c1 in rodents: effects on auditory processing, visual attention, and cortical and thalamic anatomy.

机构信息

Department of Psychology/Behavioral Neuroscience, University of Connecticut, Storrs, Conn. 06269, USA.

出版信息

Dev Neurosci. 2013;35(1):50-68. doi: 10.1159/000348431. Epub 2013 Apr 17.

Abstract

The current study investigated the behavioral and neuroanatomical effects of embryonic knockdown of the candidate dyslexia susceptibility gene (CDSG) homolog Dyx1c1 through RNA interference (RNAi) in rats. Specifically, we examined long-term effects on visual attention abilities in male rats, in addition to assessing rapid and complex auditory processing abilities in male and, for the first time, female rats. Our results replicated prior evidence of complex acoustic processing deficits in Dyx1c1 male rats and revealed new evidence of comparable deficits in Dyx1c1 female rats. Moreover, we found new evidence that knocking down Dyx1c1 produced orthogonal impairments in visual attention in the male subgroup. Stereological analyses of male brains from prior RNAi studies revealed that, despite consistent visible evidence of disruptions of neuronal migration (i.e., heterotopia), knockdown of Dyx1c1 did not significantly alter the cortical volume, hippocampal volume, or midsagittal area of the corpus callosum (measured in a separate cohort of like-treated Dyx1c1 male rats). Dyx1c1 transfection did, however, lead to significant changes in medial geniculate nucleus (MGN) anatomy, with a significant shift to smaller MGN neurons in Dyx1c1-transfected animals. Combined results provide important information about the impact of Dyx1c1 on behavioral functions that parallel domains known to be affected in language-impaired populations as well as information about widespread changes to the brain following early disruption of this CDSG.

摘要

本研究通过 RNA 干扰 (RNAi) 技术在大鼠中对候选阅读障碍易感性基因 (CDSG) 同源物 Dyx1c1 的胚胎敲低进行了行为和神经解剖学研究。具体来说,我们检测了雄性大鼠视觉注意力能力的长期影响,此外还评估了雄性大鼠(首次评估了雌性大鼠)快速而复杂的听觉处理能力。我们的结果复制了先前 Dyx1c1 雄性大鼠复杂听觉处理能力缺陷的证据,并揭示了新的证据表明 Dyx1c1 雌性大鼠也存在类似的缺陷。此外,我们发现新的证据表明,敲低 Dyx1c1 会导致雄性亚组的视觉注意力产生正交缺陷。先前 RNAi 研究中雄性大脑的体视学分析表明,尽管神经元迁移(即异位)存在明显的破坏,但 Dyx1c1 的敲低并未显著改变皮质体积、海马体积或胼胝体的中矢状面积(在另一组类似处理的 Dyx1c1 雄性大鼠中测量)。然而,Dyx1c1 的转染确实导致了内侧膝状体 (MGN) 解剖结构的显著变化,Dyx1c1 转染动物的 MGN 神经元明显变小。综合结果提供了有关 Dyx1c1 对行为功能的影响的重要信息,这些行为功能与语言障碍人群中已知受影响的领域相平行,以及在早期破坏这个 CDSG 后大脑广泛变化的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e68/3980864/f9a7cdbf505f/nihms-497069-f0001.jpg

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