BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice.
BACE1 elevation is associated with aberrant limbic axonal sprouting in epileptic CD1 mice.
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DOI：
10.1016/j.expneurol.2012.01.003
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发表时间：
2012-05
影响因子：
5.3
通讯作者：
Patrylo, Peter R.
中科院分区：
文献类型：
--
作者：
Yan, Xiao-Xin;Cai, Yan;Zhang, Xue-Mei;Luo, Xue-Gang;Cai, Huaibin;Rose, Gregory M.;Patrylo, Peter R.
关键词：
大脑在应激和损伤后能够进行显著的突触重组，通常使用与神经发育相同的分子机制。这种形式的可塑性对于恢复和维持网络功能至关重要。然而，神经退变和随后的重组也可以在疾病的发病机制中发挥作用，就像在颞叶癫痫和阿尔茨海默病中看到的那样。β-分泌酶-1(BACE1)是一种能将β-淀粉样前体蛋白裂解成淀粉样蛋白(β-β，A-A)的水解酶。新的证据表明，BACE1还与突触可塑性和神经再生有关。在这里，我们研究了在匹罗卡品诱导的癫痫CD1小鼠中，BACE1免疫反应性(IR)是否以与癫痫发生过程中所见的突触重组一致的方式发生改变。与对照组相比，匹罗卡品致痫小鼠CA3区苔藓纤维区和齿状内分子层BACE1-IR增加，神经肽Y表达平行异常。癫痫小鼠海马区CA1区、杏仁核和颞叶皮质BACE1-IR也出现区域性增加，与生长相关蛋白43(GAP43)和多唾液酸神经细胞黏附分子(PSA-NCAM)共定位，但微管相关蛋白2(MAP2)表达减少。这些发现表明，BACE1参与了颞叶癫痫模型中边缘轴突的异常萌发，这为进一步研究BACE1在生理性和病理性神经元可塑性中的作用奠定了基础。
The brain is capable of remarkable synaptic reorganization following stress and injury, often using the same molecular machinery that governs neurodevelopment. This form of plasticity is crucial for restoring and maintaining network function. However, neurodegeneration and subsequent reorganization can also play a role in disease pathogenesis, as is seen in temporal lobe epilepsy and Alzheimer’s disease. β-Secretase-1 (BACE1) is a protease known for cleaving β-amyloid precursor protein into β-amyloid (Aβ), a major constituent in amyloid plaques. Emerging evidence suggests that BACE1 is also involved with synaptic plasticity and nerve regeneration. Here we examined whether BACE1 immunoreactivity (IR) was altered in pilocarpine-induced epileptic CD1 mice in a manner consistent with the synaptic reorganization seen during epileptogenesis. BACE1-IR increased in the CA3 mossy fiber field and dentate inner molecular layer in pilocarpine-induced epileptic mice, relative to controls (saline-treated mice and mice 24–48 h after pilocarpine-status), and paralleled aberrant expression of neuropeptide Y. Regionally increased BACE1-IR also occurred in neuropil in hippocampal area CA1 and in subregions of the amygdala and temporal cortex in epileptic mice, colocalizing with increased IR for growth associated protein 43 (GAP43) and polysialylated-neural cell adhesion molecule (PSA-NCAM), but reduced IR for microtubule-associated protein 2 (MAP2). These findings suggest that BACE1 is involved in aberrant limbic axonal sprouting in a model of temporal lobe epilepsy, warranting further investigation into the role of BACE1 in physiological vs. pathological neuronal plasticity.
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影响因子：
5.3
作者：
Borges, K;Gearing, M;Dingledine, R
通讯作者：
Dingledine, R
影响因子：
11.2
作者：
Gouras, GK;Relkin, NR;Gandy, S
通讯作者：
Gandy, S
癫痫持续时间对颞叶癫痫中脑葡萄糖代谢的影响：基于体素的映射结果。
影响因子：
2.6
作者：
Akman, Cigdem I.;Ichise, Masonori;Olsavsky, Aviva;Tikofsky, Ronald S.;Van Heerturn, Ronald L.;Gilliam, Frank
通讯作者：
Gilliam, Frank
DOI：
10.1523/jneurosci.1334-10.2010
发表时间：
2010-06-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hu X;Zhou X;He W;Yang J;Xiong W;Wong P;Wilson CG;Yan R
通讯作者：
Yan R
影响因子：
5.3
作者：
Dancause, N;Barbay, S;Nudo, RJ
通讯作者：
Nudo, RJ