Dendritic spine alterations in the hippocampus and parietal cortex of alpha7 nicotinic acetylcholine receptor knockout mice.

Dendritic spine alterations in the hippocampus and parietal cortex of alpha7 nicotinic acetylcholine receptor knockout mice.
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α7烟碱乙酰胆碱受体基因敲除小鼠海马和顶叶皮层的树突状脊柱改变。

DOI:
10.1016/j.neuroscience.2012.12.025
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发表时间:
2013-03-13
期刊:
影响因子:
3.3
通讯作者:
Mervis RF
Mervis RF
中科院分区:
医学3区
文献类型:
--
作者:
Morley BJ;Mervis RF

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α7烟碱乙酰胆碱受体(nAChR)参与高级认知和记忆功能,并且与涉及认知下降的神经系统疾病(包括阿尔茨海默病(AD))的病因学相关。我们假设α7基因敲除小鼠的脊柱变化可能有助于解释在α7基因敲除小鼠中观察到的行为缺陷和AD的前驱海马变化。我们在P24时对野生型和α7基因敲除小鼠的Golgi染色材料中小鼠海马CA 1区的树突状形态进行了定量测定。最显著的差异是基因敲除小鼠中CA 1基底树上的薄(L型)树突棘增加了64%(p <0.05)。N型(-15%)、M型(-14%)和D型(-4%)棘密度的数量略有下降。与野生型小鼠相比,基因敲除小鼠的CA 1基底树突树在靠近体部的区域分支明显较少(p <0.01),但在更远的分支中没有。在许多实验范例中已经观察到CA 1基底树突棘的配置变化,这表明基底树突棘具有高度的可塑性。认知功能障碍的一个组成部分可能是通过α7调节的GABA能中间神经元与CA 1基底树突的突触。
The α7 nicotinic acetylcholine receptor (nAChR) is involved in higher cognitive and memory functions, and is associated with the etiology of neurological diseases involving cognitive decline, including Alzheimer’s disease (AD). We hypothesized that spine changes in the α7 knockout might help to explain the behavioral deficits observed in α7 knockout mice and prodromal hippocampal changes in AD. We quantified several measures of dendritic morphology in the CA1 region of the mouse hippocampus in Golgi-stained material from wildtype and α7 knockout mice at P24. The most significant difference was a 64% increase in thin (L-type) dendritic spines on the CA1 basilar tree in knockout mice (p < .05). There were small decreases in the number of in N-type (−15%), M-type (−14%) and D-type (−4%) spine densities. The CA1 basilar dendritic tree of knockout mice had significantly less branching in the regions nearthesoma in comparison with wildtype animals (p < .01), but not in the more distal branching. Changes in the configuration of CA1 basilar dendritic spines have been observed in a number of experimental paradigms, suggesting that basilar dendritic spines are highly plastic. One component of cognitive dysfunction may be through α7-modulated GABAergic interneurons synapsing on CA1 basal dendrites.
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