Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
Authors: Carlos M Soto-Faguás
Ann Van der Jeugd
Lydia Giménez-Llort
Rudi D&#x27;Hooge
Arnaldo Parra-Damas
Tariq Ahmed
Carlos A Saura
Frank M LaFerla
Raquel Baeta-Corral
Journal: Scientific reports (2018)
Discipline: Multidisciplinary
Keywords: amyloid-β plaques; tau; Alzheimer's disease; antioxidants; selenium
Affiliations: Laboratory of Biological Psychology, Katholieke Universiteit Leuven, Leuven, 3000, Belgium., Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain., Institut de Neurociències, Departament de Psiquiatria i Medicina Legal, Unitat de Psicologia Mèdica, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain., Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar., Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, 92697, CA, USA., Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain. .

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. 

Retracted: No

PubPeer comments:
 Figure 5a appears to have two images which overlap. *** Enhanced contrast ![file] , 
 ![file] Thanks for the comment. The two immunohistochemical images are captured from the same vehicle-treated 3xTg-AD mouse that is the reason that the two images overlap. The first image corresponds to the CA1 hippocampal region quantified at the bottom, being the red marked region the CA1 pyramidal neuron layer. The last image (CC) corresponds to the corpus callosum (CC; upper part of the image; green marked square) from the same animal but also shows the CA1 region (lower part of the image; red marked square). The CC region is anatomically located in the mouse brain just above the CA1 pyramidal layer (as shown in greensquare in the attached image), so that is the reason that both images show the same CA1 region (red marked square) because they are from the same animal, and CA1 region is located at the bottom of the CC. ,