期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 51, 期 1, 页码 69-79出版社
IOS PRESS
DOI: 10.3233/JAD-150975
关键词
Activity regulated cytoskeletal-associated protein; Alzheimer's disease; hippocampus; memory; neuroplasticity
资金
- CONACYT [CB2012/178841]
- Programa de Becas de Estancias Posdoctorales, Doctorado en Ciencias Biologicas y de la Salud, Universidad Autonoma Metropolitana (UAM)
- DGAPA-UNAM [IN201613, IN209413]
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 (similar to 4-fold) increment in the percentage of Arc+ cells in the CA3 region of the 10-month-old wildtype 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-beta were much more likely to express Arc protein under basal conditions. We propose that in 3xTg-AD mice, intraneuronal amyloid-beta expression in CA3 could increase unspecific neuronal activation and subsequent Arc protein expression, which might impair further memory-stabilizing processes.
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