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

Knockdown of the candidate dyslexia susceptibility gene homolog dyx1c1 in rodents: effects on auditory processing, visual attention, and cortical and thalamic anatomy.
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DOI:
10.1159/000348431
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发表时间:
2013
影响因子:
2.9
通讯作者:
Fitch RH
Fitch RH
中科院分区:
医学3区
文献类型:
--
作者:
Szalkowski CE;Booker AB;Truong DT;Threlkeld SW;Rosen GD;Fitch RH

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本研究通过RNA干扰研究了胚胎敲除候选阅读障碍易感基因(CDSG)同源物Dyx1c1对大鼠行为和神经解剖学的影响。具体来说,除了评估雄性大鼠和首次评估雌性大鼠的快速和复杂听觉处理能力外,我们还研究了对雄性大鼠视觉注意力能力的长期影响。结果重复了Dyx1c1雄性大鼠复杂声学处理缺陷的先前证据,并揭示了Dyx1c1雌性大鼠类似缺陷的新证据。此外,我们发现新的证据表明,在男性亚组中,敲除Dyx1c1会产生视觉注意的正交损伤。来自先前RNA干扰研究的雄性大脑的立体学分析显示,尽管有一致的可见证据表明神经元迁移受到破坏(即异位),但敲低Dyx1c1并没有显著改变皮质体积、海马体积或胼胝体正中矢状区(在一个单独的Dyx1c1雄性大鼠队列中测量)。然而,Dyx1c1转染确实导致内侧膝状核(MGN)解剖结构发生显著变化,Dyx1c1转染动物的内侧膝状核神经元明显转向较小的MGN神经元。综合结果提供了关于Dyx1c1对行为功能的影响的重要信息,这些平行结构域已知在语言障碍人群中受到影响,以及关于该候选阅读障碍易感基因早期破坏后大脑广泛变化的信息。
The current study investigated the behavioral and neuroanatomical effects of embryonic knockdown of the candidate dyslexia susceptibility gene (CDSG) homolog Dyx1c1 through RNA interference in rats. Specifically, we examined long-term effects on visual attention abilities in males, in addition to assessing rapid and complex auditory processing abilities in male and, for the first time, female rats. 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 sub-group. Stereological analyses of male brains from prior RNA interference studies revealed that, despite consistent visible evidence of disruptions in neuronal migration (i.e., heterotopia), knockdown of Dyx1c1 did not significantly alter 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 candidate dyslexia susceptibility gene.
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