title: Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.
abstract: The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer's disease. A mouse model which simulates amyloid-β (Aβ) neuropathology, the Tg2576 mouse, was used to address these early changes. Here, we show EC abnormalities occur in 2- to 4-month-old Tg2576 mice, an age before Aβ deposition and where previous studies suggest that there are few behavioral impairments. First we show, using a sandwich enzyme-linked immunosorbent assay, that soluble human Aβ40 and Aβ42 are detectable in the EC of 2-month-old Tg2576 mice before Aβ deposition. We then demonstrate that 2- to 4-month-old Tg2576 mice are impaired at object placement, an EC-dependent cognitive task. Next, we show that defects in neuronal nuclear antigen expression and myelin uptake occur in the superficial layers of the EC in 2- to 4-month-old Tg2576 mice. In slices from Tg2576 mice that contained the EC, there were repetitive field potentials evoked by a single stimulus to the underlying white matter, and a greater response to reduced extracellular magnesium ([Mg(2+)]o), suggesting increased excitability. However, deep layer neurons in Tg2576 mice had longer latencies to antidromic activation than wild type mice. The results show changes in the EC at early ages and suggest that altered excitability occurs before extensive plaque pathology.
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, New York, NY, USA; Department of Child & Adolescent Psychiatry, New York University Langone Medical Center, New York, NY, USA. Electronic address: aduffy@nki.rfmh.org.
authors.forename: Aine M
authors.initials: AM
authors.lastname: Duffy
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, New York, NY, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Morales-Corraliza
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, New York, NY, USA; Department of Physiology & Neuroscience, Sackler Institute of Graduate Biomedical Sciences, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Keria M
authors.initials: KM
authors.lastname: Bermudez-Hernandez
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, New York, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schaner
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, New York, NY, USA.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Magagna-Poveda
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, New York, NY, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mathews
authors.affiliation: Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, New York, NY, USA; Department of Child & Adolescent Psychiatry, New York University Langone Medical Center, New York, NY, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA; Department of Physiology & Neuroscience, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Scharfman
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000378:metabolism / Q000473:pathology*; D005260:Female; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D008274:Magnesium
keywords: Entorhinal cortex; Excitability; NeuN; Object placement; Prefrontal cortex; Retrosplenial cortex
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