Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice.
Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice.
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阻断烟碱乙酰胆碱受体可抑制野生型小鼠的海马长时程增强，但不会抑制 ApoE4 靶向替代小鼠的海马长时程增强。
DOI：
10.1002/jnr.20684
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Trommer,BarbaraL
中科院分区：
文献类型：
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作者：
Yun,SungHwan;Park,KyungA;Sullivan,Patrick;Pasternak,JosephF;Ladu,MaryJo;Trommer,BarbaraL
烟碱神经传递受损和apoE 4遗传均与阿尔茨海默病（AD）风险增加以及其他记忆相关行为缺陷相关。长时程增强（LTP）是一种记忆的细胞模型，已知会被烟碱类药物改变。最近的研究也支持在LTP的apoE紧急作用。我们比较了烟碱性乙酰胆碱受体（nAChR）的非特异性拮抗剂美加明对野生型（wt）小鼠和表达人apoE 4的靶向替代小鼠（apoE 4-TR）海马切片中基础突触传递和LTP的影响。在齿状回（DG）记录对内侧穿通通路激活的场兴奋性突触后电位（EPSP），并使用θ爆发刺激诱导LTP。美卡拉明（3 μM）的水浴应用未改变两种小鼠品系的输入-输出关系或成对脉冲抑制。在对照条件下，apoE 4-TR小鼠的LTP显著低于野生型小鼠（17.5% ± 3.2%，n = 9，vs. 30.1% ± 3.9%，n = 11，P< 0.02）。美加明将野生型小鼠的LTP降低至与apoE 4-TR小鼠的对照水平相似的水平（15.7% ± 3.4%，n = 9），而apoE 4-TR未显示美加明进一步降低LTP（16.6% ± 3.7%，n = 8）。因此，表达人apoE 4的小鼠与野生型小鼠在LTP能力和烟碱胆碱能阻断对LTP的影响方面都不同。在apoE 4-TR小鼠中，烟碱神经传递可能已经受损，因此，干扰这种胆碱能系统的完整性代表了apoE 4等位基因遗传导致认知风险的机制。© 2005 Wiley利斯公司
Both impaired nicotinic neurotransmission and the inheritance of apoE4 are associated with increased risk for Alzheimer disease (AD) as well as other deficiencies in memory‐related behavior. Long‐term potentiation (LTP), a cellular model of memory, is known to be altered by nicotinic agents. Recent studies also support an emergent role for apoE in LTP. We compared the effects of mecamylamine, a nonspecific antagonist of nicotinic acetylcholine receptors (nAChRs), on basal synaptic transmission and LTP in hippocampal slices from wild‐type (wt) mice and targeted replacement mice expressing human apoE4 (apoE4‐TR). Field excitatory postsynaptic potentials (EPSPs) were recorded in the dentate gyrus (DG) in response to medial perforant path activation, and theta burst stimulation was used to induce LTP. Bath application of mecamylamine (3 μM) did not alter input–output relationships or paired pulse depression in either mouse strain. Under control conditions, apoE4‐TR mice showed significantly less LTP than wt mice (17.5% ± 3.2%, n = 9, vs. 30.1% ± 3.9%, n = 11,P< 0.02). Mecamylamine reduced LTP in wt mice to a level that was similar to control levels for apoE4‐TR mice (15.7% ± 3.4%, n = 9), whereas apoE4‐TR showed no further reduction of LTP (16.6% ± 3.7%, n = 8) by mecamylamine. Thus mice expressing human apoE4 differ from wt mice both in their capacity for LTP and in the effect on LTP of nicotinic cholinergic blockade. It is possible that nicotinic neurotransmission is already compromised in apoE4‐TR mice and, hence, that interference with the integrity of this cholinergic system represents a mechanism by which inheritance of the apoE4 allele contributes to cognitive risk. © 2005 Wiley‐Liss, Inc.