Department of Physiology and Biophysics, College of Medicine, Eulji University, Daejeon, Republic of Korea.
Neurosci Lett. 2011 Nov 7;505(1):6-9. doi: 10.1016/j.neulet.2011.05.246. Epub 2011 Jul 20.
Neuregulin-1 (NRG1) participates in numerous neurodevelopmental processes and plasticity of the brain. Despite this, little is known about its role in Alzheimer's disease (AD). Amyloid β (Aβ) peptide is generally believed to play a critical role in the pathogenesis of AD. The present study examined the effect of synthetic Aβ₁₋₄₂ peptides on long-term potentiation (LTP) in the CA1 region of mice hippocampal slices, a cellular model of learning and memory. We found that application of a test dose of Aβ₁₋₄₂ (200 nM) significantly inhibited the development of LTP without affecting basal synaptic transmission. Pretreatment with NRG1 effectively prevented Aβ₁₋₄₂-induced impairment of LTP, an effect that was dose-dependent. This LTP-restoring action of NRG1 was almost completely abolished by blocking ErbB4, a key NRG1 receptor, suggesting that NRG1 acts through ErbB4 to exert its protective action on LTP. The present study thus provides the first demonstration that NRG1/ErbB4 protects against Aβ-induced hippocampal LTP impairment, suggesting that NRG1 may be a promising candidate for the treatment of early-stage AD.
神经调节蛋白-1（NRG1）参与了许多神经发育过程和大脑的可塑性。尽管如此，人们对其在阿尔茨海默病（AD）中的作用知之甚少。淀粉样β（Aβ）肽通常被认为在 AD 的发病机制中起关键作用。本研究检查了合成 Aβ₁₋₄₂肽对小鼠海马切片 CA1 区的长时程增强（LTP）的影响，LTP 是学习和记忆的细胞模型。我们发现，应用 Aβ₁₋₄₂（200 nM）测试剂量可显著抑制 LTP 的发展，而不影响基础突触传递。NRG1 的预处理可有效防止 Aβ₁₋₄₂诱导的 LTP 损伤，其作用呈剂量依赖性。NRG1 对 LTP 的这种恢复作用几乎完全被阻断 ErbB4 （NRG1 的关键受体）所消除，这表明 NRG1 通过 ErbB4 发挥其对 LTP 的保护作用。因此，本研究首次证明 NRG1/ErbB4 可防止 Aβ 诱导的海马 LTP 损伤，提示 NRG1 可能是治疗早期 AD 的有希望的候选药物。
