Defining pre-synaptic nicotinic receptors regulated by beta amyloid in mouse cortex and hippocampus with receptor null mutants.
Defining pre-synaptic nicotinic receptors regulated by beta amyloid in mouse cortex and hippocampus with receptor null mutants.
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DOI：
10.1111/j.1471-4159.2009.06070.x
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发表时间：
2009-06
影响因子：
4.7
通讯作者：
Nichols RA
中科院分区：
文献类型：
--
作者：
Mehta TK;Dougherty JJ;Wu J;Choi CH;Khan GM;Nichols RA
可溶性β-淀粉样蛋白对神经元信号传导的破坏与阿尔茨海默病早期的短期记忆缺陷有关。β-淀粉样蛋白的一个潜在靶点是突触，有证据表明与突触前和突触后元件的差异相互作用。我们先前的工作揭示了pM-nM可溶性β-淀粉样蛋白对分离的突触前末梢的激动剂样作用，以增加[Ca 2 +]i，突触前烟碱受体明显参与。为了直接确定烟碱受体在突触前Ca 2+调节中的作用，我们研究了β-淀粉样蛋白对从携带β2或α7烟碱受体无效突变体（敲除）的小鼠中分离的终末的突触前作用。α7基因敲除小鼠海马终末对β-淀粉样蛋白的平均突触前反应没有变化，而β2基因敲除小鼠海马终末的反应强烈减弱。相反，α7基因敲除小鼠的皮质终末对可溶性β-淀粉样蛋白的突触前反应强烈减弱，而β2基因敲除小鼠的皮质终末对可溶性β-淀粉样蛋白的突触前反应中度减弱。后者的反应，具有不同的动力学，完全阻断α-银环蛇毒素。因此，受体无效突变体的使用允许直接证明特异性烟碱受体参与可溶性β-淀粉样蛋白对突触前Ca 2+的调节，并且还表明海马和皮质中β-淀粉样蛋白对突触的不同神经调节。
Disruption of neuronal signaling by soluble β-amyloid has been implicated in deficits in short-term recall in the early stages of Alzheimer's disease. One potential target for β-amyloid is the synapse, with evidence for differential interaction with both pre- and postsynaptic elements. Our previous work revealed an agonist-like action of pM-nM soluble β-amyloid on isolated presynaptic terminals to increase [Ca2+]i, with apparent involvement of presynaptic nicotinic receptors. To directly establish the role of nicotinic receptors in presynaptic Ca2+ regulation, we investigated the presynaptic action of β-amyloid on terminals isolated from mice harboring either β2 or α7 nicotinic receptor null mutants (knockouts). Average presynaptic responses to β-amyloid in hippocampal terminals of α7 knockout mice were unchanged, whereas responses in hippocampal terminals from β2 knockout mice were strongly attenuated. In contrast, presynaptic responses to soluble β-amyloid were strongly attenuated in cortical terminals from α7 knockout mice, but were moderately attenuated in cortical terminals from β2 knockout mice. The latter responses, having distinct kinetics, were completely blocked by α-bungarotoxin. The use of receptor null mutants thus permitted direct demonstration of the involvement of specific nicotinic receptors in presynaptic Ca2+ regulation by soluble β-amyloid, and also indicated differential neuromodulation by β-amyloid of synapses in hippocampus and cortex.
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影响因子：
4.2
作者：
Ashenafi, S;Fuente, A;Yajeya, J
通讯作者：
Yajeya, J
影响因子：
16.2
作者：
Kamenetz, F;Tomita, T;Malinow, R
通讯作者：
Malinow, R
影响因子：
82.9
作者：
Bateman, Randall J.;Munsell, Ling Y.;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
64.8
作者：
Gray, R;Rajan, AS;Dani, JA
通讯作者：
Dani, JA
DOI：
10.1523/jneurosci.3952-08.2009
发表时间：
2009-01-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Liu Q;Huang Y;Xue F;Simard A;DeChon J;Li G;Zhang J;Lucero L;Wang M;Sierks M;Hu G;Chang Y;Lukas RJ;Wu J
通讯作者：
Wu J