Cognitive impairment in the 3xTg-AD mouse model of Alzheimer's disease is reduced by Abeta-immunotherapy and cognitive stimulation
Ramos Roda, Alejandro (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Esquerda-Canals, Gisela (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Martí-Clúa, Joaquín (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Villegas Hernández, Sandra (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2020
Abstract:	Clinical symptoms of Alzheimer's Disease (AD) include behavioral alterations and cognitive impairment. These functional phenotypes early occur in triple-transgenic (3xTg-AD) mice. Specifically, behavioral alterations are first detected when mice are at around 2. 5 months old and cognitive impairment in between 3- and 5-month-old mice. In this work, the effect of chronic Aβ-immunotherapy on behavioral and cognitive abilities was tested by monthly administering the antibody fragment scFv-h3D6 to 3xTg-AD female mice from 5 to 9 months of age. An untreated group was used as a reference, as well as to attain some information on the effect of training during the longitudinal study. Behavioral and psychological symptoms of dementia (BPSD)-like symptoms were already evident in 5-month-old mice, in the form of neophobia and anxious-like behavior. The exploratory activity decreased over the longitudinal study, not only for 3xTgAD mice but also for the corresponding non-transgenic mice (NTg). Learning abilities of 3xTg-AD mice were not seriously compromised but an impairment in long-term spatial memory was evident at 5 months of age. Interestingly, scFv-h3D6-treatment affected the cognitive impairment displayed by 5-month-old 3xTg-AD mice. It is worth noting that training also reduced cognitive impairment of 3xTg-AD mice over the longitudinal study, suggesting that to properly quantify the isolated therapeutic potential of any drug on cognition using this model it is convenient to perform a prompt, age-matched study rather than a longitudinal study. In addition, a combination of both training and Aβ-immunotherapy could constitute a possible approach to treat Alzheimer's disease.
Grants:	Agencia Estatal de Investigación SAF2017-89613R
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
Subject:	Aβ ; Tau ; Immunotherapy ; Alzheimer ; ScFv ; 3xTg-AD ; Training
Published in:	Pharmaceutics, Vol. 12, Num. 10 (October 2020) , art. 944, ISSN 1999-4923

DOI: 10.3390/pharmaceutics12100944
PMID: 33023109

21 p, 2.6 MB

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