Senescence-Accelerated Mice P8: A Tool to Study Brain Aging and Alzheimer's Disease in a Mouse Model

Abstract

The causes of aging remain unknown, but they are probably intimately linked to a multifactorial process that affects cell networks to varying degrees. Although a growing number of aging and Alzheimer's disease (AD) animal models are available, a more comprehensive and physiological mouse model is required. In this context, the senescence-accelerated mouse prone 8 (SAMP8) has a number of advantages, since its rapid physiological senescence means that it has about half the normal lifespan of a rodent. In addition, according to data gathered over the last five years, some of its behavioral traits and histopathology resemble AD human dementia. SAMP8 has remarkable pathological similarities to AD and may prove to be an excellent model for acquiring more in-depth knowledge of the age-related neurodegenerative processes behind brain senescence and AD in particular. We review these facts and particularly the data on parameters related to neurodegeneration. SAMP8 also shows signs of aging in the immune, vascular, and metabolic systems, among others.

Periodontal disease, tooth loss and dementia: Is there a link? A systematic review

“…Although the murine model has been used for several decades in ageing research, the senescence‐accelerated mouse prone 8 (SAMP8) has the advantage of rapid ageing due to accelerated physiological senescence, causing its lifespan to be an average of 12 months, that is about half of that of a rodent . Further, some ageing behavioural characteristics and histopathology resemble those of Alzheimer's disease in humans . Studies have used SAMP8 mice of young‐, middle‐ and old‐age groups to demonstrate the varying effects of tooth loss at different ages .…”

Nodes and biological processes identified on the basis of network analysis in the brain of the senescence accelerated mice as an Alzheimer's disease animal model

“…Its progression in late-onset AD studies is fundamentally limited by our reliance on mouse models of severe familial/early-onset AD (Zhang et al, 2013). SAMP8 mice, a spontaneous animal model of accelerated aging and harboring the behavioral and histopathological signatures of AD, may more closely represent the complexity of the disease compared to the gene-modified model due to its multifactorial nature of late-onset or age-related sporadic AD (Pang et al, 2006; Pallas et al, 2008; Woodruff-Pak, 2008; Tomobe and Nomura, 2009; Morley et al, 2012; Pallàs, 2012). Thus, understanding the underpinnings of the AD-like phenotype in SAMP8 mice is essential for developing and evaluating therapeutic approaches for this widespread and devastating insidious disease.…”

“…Studies aimed at identifying the mechanisms associated with AD and new therapeutic treatments are currently being performed in rodent models of AD. Using SAM/resistant-1 (SAMR1) as a control, the senescence accelerated mouse prone-8 (SAMP8) is a robust model of AD because it shares phenotypes that resemble the symptoms of late-onset and age-related sporadic AD patients and because has distinct advantages over the gene-modified model (Pang et al, 2006; Pallas et al, 2008; Woodruff-Pak, 2008; Tomobe and Nomura, 2009; Morley et al, 2012; Pallàs, 2012). Although investigators have developed new therapies and have tested in detail, the structural (Gutierrez-Cuesta et al, 2007; del Valle et al, 2012; Li et al, 2012), functional (Sureda et al, 2006; Tajes et al, 2008; Lou et al, 2012; Yamaguchi et al, 2012) and behavioral consequences (Gong et al, 2008; Shi et al, 2010b; Shih et al, 2010; Chang et al, 2012; Kanno et al, 2012; Lopez-Ramos et al, 2012; Lou et al, 2012; Orejana et al, 2012; Dobarro et al, 2013; Huang et al, 2013; Sawano et al, 2013) of AD-associated pathology based on SAMP8 mice, little progress has been made with regard to the patho-physiological mechanisms of SAMP8 mice, and the underlying causes of the AD-like phenotype in SAMP8 mice remain unknown.…”

Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for Alzheimer’s Disease

“…The Senescence-Accelerated Prone Mouse 8 (SAMP8), a non-transgenic mouse, was established through phenotypic selection of the AKR/J mice strain and is an attractive model to study aging processes and, specially, age-related deterioration in learning and memory, emotional disorders and neurochemical alterations around 5 months of age (39)(40)(41). Some of the changes in the mice are directly related to AD such as APP processing alteration and Tau hyperphosphorylation (42).…”