title: Neuregulin-1 prevents amyloid β-induced impairment of long-term potentiation in hippocampal slices via ErbB4.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: Sun Seek
authors.initials: SS
authors.lastname: Min
authors.forename: Jihua
authors.initials: J
authors.lastname: An
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Lee
authors.forename: Geun Hee
authors.initials: GH
authors.lastname: Seol
authors.forename: Jae Hyeung
authors.initials: JH
authors.lastname: Im
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Tai-Kyoung
authors.initials: TK
authors.lastname: Baik
authors.forename: Ran-Sook
authors.initials: RS
authors.lastname: Woo
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020890:Neuregulin-1 / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D066247:Receptor, ErbB-4
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D020890:Neuregulin-1; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4