The long-lived Octodon degus as a rodent drug discovery model for Alzheimer's and other age-related diseases

Abstract

Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disease. Despite decades of research, no disease modifying therapy is available and a change of research objectives and/or development of novel research tools may be required. Much AD research has been based on experimental models using animals with a short lifespan that have been extensively genetically manipulated and do not represent the full spectrum of late-onset AD, which make up the majority of cases. The aetiology of AD is heterogeneous and involves multiple factors associated with the late-onset of the disease like disturbances in brain insulin, oxidative stress, neuroinflammation, metabolic syndrome, retinal degeneration and sleep disturbances which are all progressive abnormalities that could account for many molecular, biochemical and histopathological lesions found in brain from patients dying from AD. This review is based on the long-lived rodent Octodon degus (degu) which is a small diurnal rodent native to South America that can spontaneously develop cognitive decline with concomitant phospho-tau, β-amyloid pathology and neuroinflammation in brain. In addition, the degu can also develop several other conditions like type 2 diabetes, macular and retinal degeneration and atherosclerosis, conditions that are often associated with aging and are often comorbid with AD. Long-lived animals like the degu may provide a more realistic model to study late onset AD.

Strengths and Weaknesses of the Gray Mouse Lemur (Microcebus murinus) as a Model for the Behavioral and Psychological Symptoms and Neuropsychiatric Symptoms of Dementia

“…This similarity is not found in most rodents, whose memory function does not match that of humans (Deacon, 2014). One specific rodent species, Octodon degus , has more similarities with humans and can provide benefits in aging studies (Tarragon et al, 2013; Hurley et al, 2018). In most tasks, the acquisition of the rule is not impacted by aging (Picq, 1998; Picq and Dhenain, 1998), and cognitive processes involved in simple stimulus-reward association performances are preserved during aging (Joly et al, 2006; Picq, 2007).…”

Editorial: Human and Animal Models for Translational Research on Neurodegeneration: Challenges and Opportunities From South America

“…Preclinical testing of new therapeutic concepts has been difficult due to the lack of naturally occurring disease models. Although availability of genetically engineered mouse models has partly addressed this challenge, neurodegenerative diseases rarely occur in non-human animals (Jucker, 2010 ); and the causes of non-familial dementia are multifactorial and age-related (Hurley et al, 2018 ). In consequence, non-genetic and natural models of dementia are still required.…”

“…Advances could be made by studying species such as the Octodon degus , an endemic rodent from Chile that spontaneously develops an analog of dementia at behavioral and neurobiological levels (Ardiles et al, 2012 ; Hurley et al, 2018 ). In addition, the O. degus can also naturally develop several other conditions like diabetes mellitus type 2, macular and retinal degeneration and atherosclerosis, conditions that are often associated with aging and comorbid disorders with dementia (Hurley et al, 2018 ). Consequently, the O. degus is a suitable novel experimental model that can be utilized for the development of disease-modifying treatments for dementia.…”

Human and Animal Models for Translational Research on Neurodegeneration: Challenges and Opportunities From South America

“…Preclinical testing of new therapeutic concepts has been difficult due to the lack of naturally occurring disease models. Although availability of genetically engineered mouse models has partly addressed this challenge, neurodegenerative diseases rarely occur in non-human animals (Jucker, 2010); and the causes of non-familial dementia are multifactorial and agerelated (Hurley et al, 2018). In consequence, non-genetic and natural models of dementia are still required.…”