Fluorocitrate induced the alterations of memory-related proteins and tau hyperphosphorylation in SD rats

Fluorocitrate induced the alterations of memory-related proteins and tau hyperphosphorylation in SD rats
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氟柠檬酸诱导 SD 大鼠记忆相关蛋白和 tau 蛋白过度磷酸化的改变

DOI:
10.1016/j.neulet.2014.10.036
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发表时间:
2015-01
期刊:
Neurosci Lett
影响因子:
--
通讯作者:
Liu, Gong-Ping
Liu, Gong-Ping
中科院分区:
其他
文献类型:
--
作者:
Wang, Qun;Zhang, Jia-Yu;Wang, Jian-Zhi;Liu, Gong-Ping

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星形胶质细胞为神经元提供结构、代谢和营养支持。然而,至今还没有直接证据表明星形胶质细胞是否参与了突触蛋白表达和tau蛋白磷酸化的调节。在此,我们将1 nmol氟柠檬酸(FC)注射到SD大鼠左侧脑室1 h,FC优先被星形胶质细胞摄取并导致星形胶质细胞三羧酸循环的可逆抑制,发现FC治疗降低了几种记忆相关蛋白的水平,如AMPA受体GluR 1/2,突触后密度蛋白93/95,Arc和磷酸化cAMP反应元件结合蛋白,同时增加海马突触素和突触素I水平。FC处理还增加了多个阿尔茨海默病相关磷酸化位点的磷酸化tau水平,以及糖原合成酶激酶-3 β的激活和蛋白磷酸酶-2A的失活。在原代海马神经元中也观察到类似的作用,所述原代海马神经元与来自FC处理的原代星形胶质细胞的条件培养基一起培养。我们的数据表明,星形胶质细胞调节神经元tau蛋白磷酸化和几种突触蛋白的表达。
Astrocytes provide structural, metabolic and trophic supports for neurons. However, there are no direct evidences whether astrocytes involve in the regulation of synaptic proteins expression and tau phosphorylation until now. Here, we injected 1 nmol fluorocitrate (FC), which preferentially taken up by astrocytes and results in reversible inhibition of the astrocytic tricarboxylic acid cycle, into the left lateral ventricle of the brain in the SD rats for 1 h, and found that FC treatment decreased several memory-related proteins levels, such as AMPA receptor GluR1/2, postsynaptic density protein 93/95, Arc and phosphorylated cAMP response element binding proteins, while increased synaptophysin and synapsin I levels in the hippocampus. FC treatment also increased the levels of phosphorylated tau at multiple Alzheimer-related phosphorylation sites, as well as activation of glycogen synthase kinase-3β and inactivation of protein phosphatase-2A. Similar effects were also observed in the primary hippocampal neurons, which were cultured with the conditioned media from FC-treatment primary astrocytes. Our data suggest that astrocytes regulate neuronal tau phosphorylation and several synaptic proteins expression.
AMPA 受体递送至突触周围位点先于长时程增强的完全表达。
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