Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
Van der Jeugd, Ann (Katholieke Universiteit Leuven)
Parra-Damas, Arnaldo (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Baeta Corral, Raquel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Soto-Faguás, Carlos M. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ahmed, Tariq (Hamad Bin Khalifa University)
LaFerla, Frank M. (University of California)
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
D'Hooge, Rudi (Katholieke Universiteit Leuven)
Saura Antolín, Carlos (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2018
Abstract:	Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimer's disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12-14 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number of aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.
Grants:	Generalitat de Catalunya 2012FIB100198 Generalitat de Catalunya 2017FIB00326 Ministerio de Sanidad y Consumo CB06/05/0042 Ministerio de Ciencia e Innovación BES-2011-044405 Instituto de Salud Carlos III AES-PI10/00283 Ministerio de Sanidad y Consumo SAF2016-80027-R European Commission 200611
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 8 (april 2018) , ISSN 2045-2322

DOI: 10.1038/s41598-018-24741-0
PMID: 29691439

12 p, 9.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
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