Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome.
Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome.
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DOI：
10.1371/journal.pone.0078561
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Guillemot F
中科院分区：
文献类型：
--
作者：
Haas MA;Bell D;Slender A;Lana-Elola E;Watson-Scales S;Fisher EM;Tybulewicz VL;Guillemot F
唐氏综合征（DS）是一种高度流行的发育障碍，影响1/700的新生儿。影响学习和记忆的智力残疾在所有情况下都存在，表现为智商低于平均水平。我们试图确定是否有缺陷的形态和大脑皮层神经元的连接可能是认知缺陷的基础，已被描述在两个小鼠模型的DS，Tc 1和Ts 1 Rhr小鼠线。我们利用子宫内电穿孔标记一组未来的上层投射神经元在大脑皮层的发育小鼠胚胎与GFP，然后检查神经元的定位和形态在成年早期，这表明没有改变皮质层的位置或形态在Tc 1或Ts 1 Rhr小鼠皮质。树突的数量，以及树突的长度和分支是正常的DS模型，与野生型对照。投射神经元突触输入的网站，树突棘，在Tc 1和Ts 1 Rhr皮质在出生后三周和三个月进行了分析，并观察到在两个小鼠线的脊柱形态的显着变化。Ts 1 Rhr小鼠在三周大时的薄棘明显较少。在三个月大时，Tc 1小鼠的蘑菇刺明显较少--这种形态与建立的突触输入和学习记忆有关。蘑菇刺的减少伴随着蘑菇刺数量的显著增加。这些数据表明树突棘异常可能是DS模型中认知缺陷的更重要因素，而不是整体神经元结构缺陷。
Down Syndrome (DS) is a highly prevalent developmental disorder, affecting 1/700 births. Intellectual disability, which affects learning and memory, is present in all cases and is reflected by below average IQ. We sought to determine whether defective morphology and connectivity in neurons of the cerebral cortex may underlie the cognitive deficits that have been described in two mouse models of DS, the Tc1 and Ts1Rhr mouse lines. We utilised in utero electroporation to label a cohort of future upper layer projection neurons in the cerebral cortex of developing mouse embryos with GFP, and then examined neuronal positioning and morphology in early adulthood, which revealed no alterations in cortical layer position or morphology in either Tc1 or Ts1Rhr mouse cortex. The number of dendrites, as well as dendrite length and branching was normal in both DS models, compared with wildtype controls. The sites of projection neuron synaptic inputs, dendritic spines, were analysed in Tc1 and Ts1Rhr cortex at three weeks and three months after birth, and significant changes in spine morphology were observed in both mouse lines. Ts1Rhr mice had significantly fewer thin spines at three weeks of age. At three months of age Tc1 mice had significantly fewer mushroom spines - the morphology associated with established synaptic inputs and learning and memory. The decrease in mushroom spines was accompanied by a significant increase in the number of stubby spines. This data suggests that dendritic spine abnormalities may be a more important contributor to cognitive deficits in DS models, rather than overall neuronal architecture defects.
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影响因子：
2.5
作者：
Belichenko, PV;Masliah, E;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
10.8
作者：
Dunlevy, Louisa;Bennett, Mike;Mohun, Timothy
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影响因子：
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作者：
ALLINQUANT, B;HANTRAYE, P;PROCHIANTZ, A
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PROCHIANTZ, A
DOI：
10.1073/pnas.0904397106
发表时间：
2009-10-06
影响因子：
11.1
作者：
Chang, Karen T.;Min, Kyung-Tai
通讯作者：
Min, Kyung-Tai
影响因子：
2.5
作者：
Belichenko, Pavel V.;Klescrevnikov, Alexander M.;Mobley, William C.
通讯作者：
Mobley, William C.