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

Article type: Research Article

Authors: Morin, Jean-Pascal^{a; b; 1} | Cerón-Solano, Giovanni^b | Velázquez-Campos, Giovanna^b | Pacheco-López, Gustavo^{a; c} | Bermúdez-Rattoni, Federico^d | Díaz-Cintra, Sofía^{b; *}

Affiliations: [a] Departamento de Ciencias de la Salud, Unidad Lerma, Universidad Autónoma Metropolitana (UAM), Lerma, Edo. Mex., México | [b] Departamento de Neurofisiología y Desarrollo, Instituto de Neurobiología (INB), Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Querétaro, Querétaro, México | [c] Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, University of Leiden, AK Leiden, The Netherlands | [d] División de Neurociencias, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México, Ciudad Universitaria, Distrito Federal, México

Correspondence: [*] Correspondence to: Sofía Díaz-Cintra, Instituto de Neurobiología, Campus Juriquilla, UNAM Boulevard Juriquilla 3001, Querétaro 76230, México. Tel.: +52 442 238 1058; Fax: + 52 442 238 1038; E-mail: yoldi@unam.mx.

Note: [1] Current address: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

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.

Keywords: Activity regulated cytoskeletal-associated protein, Alzheimer’s disease, hippocampus, memory, neuroplasticity

DOI: 10.3233/JAD-150975

Journal: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 69-79, 2016