title: The reemergence of long-term potentiation in aged Alzheimer's disease mouse model.
abstract: Mouse models of Alzheimer's disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6-7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14-19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons.
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.
authors.forename: Seonghoo
authors.initials: S
authors.lastname: Huh
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.|Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Soo-Ji
authors.initials: SJ
authors.lastname: Baek
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.|Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Health Sciences, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Whitcomb
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.|Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.|Department of Neurology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Jo
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.|Department of Neurology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Seong-Min
authors.initials: SM
authors.lastname: Choi
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences and Dong-A Anti-aging Research Center, Dong-A University, Busan 49315, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.|Department of Neurology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: National Research Center for Dementia, Gwangju 61452, Republic of Korea.
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Gwangju 61469, Republic of Korea.|Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.|Department of Neurology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.|National Research Center for Dementia, Gwangju 61452, Republic of Korea.
authors.forename: Byeong C
authors.initials: BC
authors.lastname: Kim
mesh_terms: D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000503:physiopathology; D008822:Mice, Transgenic; D020890:Neuregulin-1 / Q000378:metabolism; D009473:Neuronal Plasticity; D010320:Parvalbumins / Q000378:metabolism; D021641:Recognition, Psychology
chemical_list: D020890:Neuregulin-1; D010320:Parvalbumins; D066246:ErbB Receptors