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首页> 外文期刊>The European Journal of Neuroscience >Failure of nicotine-dependent enhancement of synaptic efficacy at Schaffer-collateral CA1 synapses of AD11 anti-nerve growth factor transgenic mice.
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Failure of nicotine-dependent enhancement of synaptic efficacy at Schaffer-collateral CA1 synapses of AD11 anti-nerve growth factor transgenic mice.

机译：在AD11抗神经生长因子转基因小鼠的Schaffer侧CA1突触中，尼古丁依赖性突触效力增强失败。

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Alzheimer's disease is a neurodegenerative disorder characterized by neuronal loss associated with a progressive impairment of cognitive functions. Early consequences of Alzheimer's disease include deficit of cholinergic signalling in particular regions controlling memory processes, such as the cortex and hippocampus, and accumulation of beta-amyloid (Abeta) peptide in neuritic plaques. The cholinergic system depends for its integrity and function on nerve growth factor. Chronic nerve growth factor deprivation in transgenic mice (AD11) engineered to produce recombinant neutralizing anti-nerve growth factor antibodies leads to progressive age-dependent Alzheimer's-like neurodegenerative pathology similar to that found in patients with Alzheimer's disease, associated with a selective loss of cholinergic neurones in the basal forebrain. Here we show that in the hippocampus of 6-month-old AD11 mice, Abeta aggregates started appearing in the CA1 region. The accumulation of Abeta was associated with a loss of cholinergic function at CA3-CA1 synapses. Whereas in wild-type mice nicotine induced a persistent increase of synaptic efficacy via alpha7 nicotine acetylcholine receptors, in AD11 mice this alkaloid failed to modify synaptic strength. Moreover, nicotine failed to transiently enhance the frequency of spontaneous miniature glutamatergic currents (miniature excitatory postsynaptic currents) recorded from CA1 but not from CA3 pyramidal neurones of AD11 mice. However, in CA3 principal cells of AD11 mice, the potentiating effect of nicotine on miniature excitatory postsynaptic currents was prevented when Abeta peptide 1-42 was added to the extracellular solution. These data suggest that in AD11 mice, Abeta interferes with nicotine acetylcholine receptors at the level of presynaptic glutamatergic terminals, inhibiting their function possibly through calcium signalling via presynaptic alpha7 nicotine acetylcholine receptors.
机译：阿尔茨海默氏病是一种神经退行性疾病，其特征在于与认知功能进行性损害相关的神经元丢失。阿尔茨海默氏病的早期后果包括控制记忆过程（例如皮质和海马体）的特定区域胆碱能信号传导不足，以及神经淀粉样斑块中淀粉样淀粉样蛋白（Abeta）的积累。胆碱能系统的完整性和功能取决于神经生长因子。经过工程改造以生产重组中和性抗神经生长因子抗体的转基因小鼠（AD11）中的慢性神经生长因子剥夺，导致进行性年龄依赖性阿尔茨海默氏样神经退行性病变，与阿尔茨海默氏病患者相似，并选择性地丧失了胆碱能基底前脑中的神经元。在这里，我们显示在6个月大的AD11小鼠的海马中，Abeta聚集体开始出现在CA1区。 Aβ的积累与CA3-CA1突触中胆碱能功能的丧失有关。在野生型小鼠中，尼古丁通过α7烟碱乙酰胆碱受体诱导突触效力持续增加，而在AD11小鼠中，该生物碱未能改变突触强度。此外，尼古丁不能瞬时增强从CA1而非AD3小鼠的CA3锥体神经元记录的自发性微型谷氨酸能电流（微型兴奋性突触后突触电流）的频率。但是，在AD11小鼠的CA3主细胞中，将Abeta肽1-42添加到细胞外溶液中后，尼古丁对微型兴奋性突触后突触电流的增强作用被阻止。这些数据表明，在AD11小鼠中，Abeta在突触前谷氨酸能受体的水平上干扰尼古丁乙酰胆碱受体，可能通过突触前α7尼古丁乙酰胆碱受体的钙信号传导来抑制其功能。

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