Aberrant hippocampal spine morphology and impaired memory formation in neuronal platelet-derived growth factor beta-receptor lacking mice.

Aberrant hippocampal spine morphology and impaired memory formation in neuronal platelet-derived growth factor beta-receptor lacking mice.
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缺乏神经元血小板衍生生长因子β受体的小鼠海马脊柱形态异常和记忆形成受损。

DOI:
10.1002/hipo.20973
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发表时间:
2012
期刊:
影响因子:
3.5
通讯作者:
Fukunaga K.
Fukunaga K.
中科院分区:
医学3区
文献类型:
--
作者:
Shioda N;Moriguchi S;Oya T;Ishii T;Shen J;Matsushima T;Nishijo H;Sasahara M;Fukunaga K.

文献摘要

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血小板衍生生长因子(PDGF)在中枢神经系统(CNS)突触功能中的生理作用仍不清楚。在这里,我们通过条件性敲除编码PDGF受体-β(PDGFR-β)的基因来确定PDGF受体-β(PDGFR-β)在中枢神经系统中的生理作用。在海马体中,PDGFR-β 通过免疫组织化学与突触前突触素和突触后密度-95 (PSD-95) 共定位。在海马 CA1 区,PDGFR-β 敲除小鼠中突触后蛋白(包括亲旋蛋白、drebrin 和 PSD-95)的表达水平显着降低,尽管突触前突触素水平与对照组相当。有趣的是,在海马 CA1 锥体神经元中,PDGFR-β 敲除小鼠的树突棘密度与野生型小鼠相比显着降低,尽管树突棘长度和树突分支数量保持不变。与这些发现一致的是,在 PDGFR-β 敲除小鼠中发现海马长时程增强 (LTP) 和海马依赖性记忆形成受损。这些结果表明 PDGFR-β 在小鼠大脑的脊柱形态和记忆形成中发挥着关键作用。 © 2011 Wiley 期刊公司。
The physiological role of platelet‐derived growth factor (PDGF) in the central nervous system (CNS) synaptic function remains uncharacterized. Here we identify physiological roles of PDGF receptor‐β (PDGFR‐β) in the CNS by conditional knockout of the gene encoding it. In the hippocampus, PDGFR‐β colocalized immunohistochemically with both presynaptic synaptophysin and postsynaptic density‐95 (PSD‐95). In the hippocampal CA1 region, expression levels of postsynaptic proteins, including spinophilin, drebrin, and PSD‐95, were significantly decreased in PDGFR‐β knockout mice, although presynaptic synaptophysin levels remained comparable to controls. Interestingly, in hippocampal CA1 pyramidal neurons, dendritic spine density in PDGFR‐β knockout mice was significantly decreased compared with that seen in wild‐type mice, although spine length and number of dendritic branches remained unchanged. Consistent with these findings, impairment in hippocampal long‐term potentiation (LTP) and in hippocampus‐dependent memory formation were seen in PDGFR‐β knockout mice. These results suggest PDGFR‐β plays critical roles in spine morphology and memory formation in mouse brain. © 2011 Wiley Periodicals, Inc.