Gene expression parallels synaptic excitability and plasticity changes in Alzheimer's disease
Saura Antolín, Carlos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Parra-Damas, Arnaldo (Universitat Autònoma de Barcelona. Institut de Neurociències)
Enríquez-Barreto, Lilian (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2015
Resum:	Alzheimer's disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of β-amyloid and tau and synapse dysfunction in memory-related neural circuits. Pathological and functional changes in the medial temporal lobe, a region essential for explicit memory encoding, contribute to cognitive decline in AD. Surprisingly, functional imaging studies show increased activity of the hippocampus and associated cortical regions during memory tasks in presymptomatic and early AD stages, whereas brain activity declines as the disease progresses. These findings suggest an emerging scenario where early pathogenic events might increase neuronal excitability leading to enhanced brain activity before clinical manifestations of the disease, a stage that is followed by decreased brain activity as neurodegeneration progresses. The mechanisms linking pathology with synaptic excitability and plasticity changes leading to memory loss in AD remain largely unclear. Recent studies suggest that increased brain activity parallels enhanced expression of genes involved in synaptic transmission and plasticity in preclinical stages, whereas expression of synaptic and activity-dependent genes are reduced by the onset of pathological and cognitive symptoms. Here, we review recent evidences indicating a relationship between transcriptional deregulation of synaptic genes and neuronal activity and memory loss in AD and mouse models. These findings provide the basis for potential clinical applications of memory-related transcriptional programs and their regulatory mechanisms as novel biomarkers and therapeutic targets to restore brain function in AD and other cognitive disorders.
Ajuts:	Ministerio de Economía y Competitividad SAF2013-43900 Ministerio de Economía y Competitividad BES-2011-044405 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-0984
Nota:	Altres ajuts: CIBERNED CB06/05/0042 i BrightFocus Foundation (A2014417S)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article de revisió ; Article ; Versió publicada
Matèria:	Alzheimer's disease ; Memory ; Transcriptome ; Neurodegeneration ; Aβ ; Gene expression
Publicat a:	Frontiers in cellular neuroscience, Vol. 9 Núm. 318 (2015) , ISSN 1662-5102

DOI: 10.3389/fncel.2015.00318
PMID: 26379494

14 p, 2.8 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Neurociències (INc)
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