Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/68470
Title: Crtc1 activates a transcriptional program deregulated at early Alzheimer's disease-related stages
Author: Parra-Damas, A.
Valero, J.
Chen, M.
España, J.
Martín, E.
Ferrer, Isidro (Ferrer Abizanda)
Rodríguez-Alvarez, J.
Saura, C. A.
Keywords: Memòria
Malalties neurodegeneratives
Expressió gènica
Memory
Neurodegenerative Diseases
Gene expression
Issue Date: 23-Apr-2014
Publisher: The Society for Neuroscience
Abstract: Cognitive decline is associated with gene expression changes in the brain, but the transcriptional mechanisms underlying memory impairments in cognitive disorders, such as Alzheimer's disease (AD), are largely unknown. Here, we aimed to elucidate relevant mechanisms responsible for transcriptional changes underlying early memory loss in AD by examining pathological, behavioral, and transcriptomic changes in control and mutant β-amyloid precursor protein (APPSw,Ind) transgenic mice during aging. Genome-wide transcriptome analysis using mouse microarrays revealed deregulation of a gene network related with neurotransmission, synaptic plasticity, and learning/memory in the hippocampus of APPSw,Ind mice after spatial memory training. Specifically, APPSw,Ind mice show changes on a cAMP-responsive element binding protein (CREB)-regulated transcriptional program dependent on the CREB-regulated transcription coactivator-1 (Crtc1). Interestingly, synaptic activity and spatial memory induces Crtc1 dephosphorylation (Ser151), nuclear translocation, and Crtc1-dependent transcription in the hippocampus, and these events are impaired in APPSw,Ind mice at early pathological and cognitive decline stages. CRTC1-dependent genes and CRTC1 levels are reduced in human hippocampus at intermediate Braak III/IV pathological stages. Importantly, adeno-associated viral-mediated Crtc1 overexpression in the hippocampus efficiently reverses Aβ-induced spatial learning and memory deficits by restoring a specific subset of Crtc1 target genes. Our results reveal a critical role of Crtc1-dependent transcription on spatial memory formation and provide the first evidence that targeting brain transcriptome reverses memory loss in AD.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1523/JNEUROSCI.5288-13.2014
It is part of: Journal of Neuroscience, 2014, vol. 34, num. 17, p. 5776-5787
Related resource: http://dx.doi.org/10.1523/JNEUROSCI.5288-13.2014
URI: http://hdl.handle.net/2445/68470
ISSN: 0270-6474
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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