title: Neuregulin-1 attenuates cognitive function impairments in a transgenic mouse model of Alzheimer's disease.
abstract: The neuregulin (NRG) family of epidermal growth factor-related proteins is composed of a wide variety of soluble and membrane-bound proteins that exert their effects via the tyrosine kinase receptors ErbB2-ErbB4. In the nervous system, the functions of NRG1 are essential for peripheral myelination, the establishment and maintenance of neuromuscular and sensorimotor systems and the plasticity of cortical neuronal circuits. In the present study, we report that an intracerebroventricular infusion of NRG1 attenuated cognitive impairments in 13-month-old Tg2576 mice, an animal model of Alzheimer's disease (AD). In addition, according to Golgi-Cox staining, NRG1 rescued the reduction in the number of dendritic spines detected in the brains of Tg2576 mice compared with vehicle (PBS)-infused mice. This result was also corroborated in vitro as NRG1 attenuated the oligomeric amyloid beta peptide(1-42) (Aβ(1-42))-induced decrease in dendritic spine density in rat primary hippocampal neuron cultures. NRG1 also alleviated the decrease in neural differentiation induced by oligomeric Aβ(1-42) in mouse fetal neural stem cells. Collectively, these results suggest that NRG1 has a therapeutic potential for AD by alleviating the reductions in dendritic spine density and neurogenesis found in AD brains.
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: B-H
authors.initials: BH
authors.lastname: Hong
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: M
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: T-K
authors.initials: TK
authors.lastname: Baik
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: R-S
authors.initials: RS
authors.lastname: Woo
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.|Seoul National University College of Medicine, Bundang Hospital, Bundang-Gu, Sungnam, Republic of Korea.|Neuroscience Research Institute, College of Medicine, Seoul National University, 103 Daehakro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D020890:Neuregulin-1; D010446:Peptide Fragments; D011994:Recombinant Proteins; C075222:amyloid beta-protein (1-42)