Neuregulin-1 prevents amyloid beta-induced impairment of long-term potentiation in hippocampal slices via ErbB4

초록

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 eta (A beta) peptide is generally believed to play a critical role in the pathogenesis of AD. The present study examined the effect of synthetic A beta(1-42) 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 A beta(1-42) (200 nM) significantly inhibited the development of LIP without affecting basal synaptic transmission. Pretreatment with NRG1 effectively prevented A beta(1-42)-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 A beta-induced hippocampal LTP impairment, suggesting that NRG1 may be a promising candidate for the treatment of early-stage AD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

키워드