title: Spatial Memory Impairment is Associated with Intraneural Amyloid-β Immunoreactivity and Dysfunctional Arc Expression in the Hippocampal-CA3 Region of a Transgenic Mouse Model of Alzheimer's Disease.
abstract: Dysfunction of synaptic communication in cortical and hippocampal networks has been suggested as one of the neuropathological hallmarks of the early stages of Alzheimer's disease (AD). Also, several lines of evidence have linked disrupted levels of activity-regulated cytoskeletal associated protein (Arc), an immediate early gene product that plays a central role in synaptic plasticity, with AD "synaptopathy". The mapping of Arc expression patterns in brain networks has been extensively used as a marker of memory-relevant neuronal activity history. Here we evaluated basal and behavior-induced Arc expression in hippocampal networks of the 3xTg-AD mouse model of AD. The basal percentage of Arc-expressing cells in 10-month-old 3xTg-AD mice was higher than wild type in CA3 (4.88% versus 1.77% , respectively) but similar in CA1 (1.75% versus 2.75% ). Noteworthy, this difference was not observed at 3 months of age. Furthermore, although a Morris water maze test probe induced a steep (∼4-fold) increment in the percentage of Arc+ cells in the CA3 region of the 10-month-old wild-type group, no such increment was observed in age-matched 3xTg-AD, whereas the amount of Arc+ cells in CA1 increased in both groups. Further, we detected that CA3 neurons with amyloid-β were much more likely to express Arc protein under basal conditions. We propose that in 3xTg-AD mice, intraneuronal amyloid-β expression in CA3 could increase unspecific neuronal activation and subsequent Arc protein expression, which might impair further memory-stabilizing processes.
authors.affiliation: Departamento de Ciencias de la Salud, Unidad Lerma, Universidad Autónoma Metropolitana (UAM), Lerma, Edo. Mex., México.|Departamento de Neurofisiología y Desarrollo, Instituto de Neurobiología (INB), Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Querétaro, Querétaro, México.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Morin
authors.affiliation: Departamento de Neurofisiología y Desarrollo, Instituto de Neurobiología (INB), Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Querétaro, Querétaro, México.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cerón-Solano
authors.affiliation: Departamento de Neurofisiología y Desarrollo, Instituto de Neurobiología (INB), Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Querétaro, Querétaro, México.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Velázquez-Campos
authors.affiliation: Departamento de Ciencias de la Salud, Unidad Lerma, Universidad Autónoma Metropolitana (UAM), Lerma, Edo. Mex., México.|Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, University of Leiden, AK Leiden, The Netherlands.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pacheco-López
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, México.
authors.forename: Federico
authors.initials: F
authors.lastname: Bermúdez-Rattoni
authors.affiliation: Departamento de Neurofisiología y Desarrollo, Instituto de Neurobiología (INB), Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Querétaro, Querétaro, México.
authors.forename: Sofía
authors.initials: S
authors.lastname: Díaz-Cintra
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D044482:Benzeneacetamides; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D011725:Pyridines; D016875:tau Proteins / Q000235:genetics
chemical_list: C579131:2-(4-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D044482:Benzeneacetamides; D003598:Cytoskeletal Proteins; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011725:Pyridines; C092069:activity regulated cytoskeletal-associated protein; D016875:tau Proteins
keywords: Activity regulated cytoskeletal-associated protein; Alzheimer’s disease; hippocampus; memory; neuroplasticity