Title:Natural AD-Like Neuropathology in Octodon degus: Impaired Burrowing and Neuroinflammation
VOLUME: 12 ISSUE: 4
Author(s):Robert M.J. Deacon, Francisco J. Altimiras, Enrique A. Bazan-Leon, Rhada D. Pyarasani, Fabiane M. Nachtigall, Leonardo S. Santos, Anthony G. Tsolaki, Lina Pednekar, Uday Kishore, Rodolfo R. Biekofsky, Rodrigo A. Vasquez and Patricia Cogram
Affiliation:Biomedicine Division, Center for Systems Biotechnology, Fraunhofer Chile Research Foundation, Santiago, Chile.
Keywords:Alzheimer’s disease, beta-amyloid, burrowing, complement, cytokines, Octodon degus.
Abstract:Alzheimer’s disease (AD) is the most common cause of dementia, affecting more than 36
million people worldwide. Octodon degus, a South American rodent, has been found to spontaneously
develop neuropathological signs of AD, including amyloid-β (Aβ) and tau deposits, as well as a decline in cognition with
age. Firstly, the present work introduces a novel behavioral assessment for O. degus - the burrowing test - which appears
to be a useful tool for detecting neurodegeneration in the O. degus model for AD. Such characterization has potentially
wide-ranging implications, because many of these changes in species-typical behaviors are reminiscent of the impairments
in activities of daily living (ADL), so characteristic of human AD. Furthermore, the present work characterizes the ADlike
neuropathology in O. degus from a gene expression point of view, revealing a number of previously unreported AD
biomarkers, which are found in human AD: amyloid precursor protein (APP), apolipoprotein E (ApoE), oxidative stressrelated
genes from the NFE2L2 and PPAR pathway, as well as pro-inflammatory cytokines and complement proteins, in
agreement with the known link between neurodegeneration and neuroinflammation. In summary, the present results confirm
a natural neuropathology in O. degus with similar characteristics to AD at behavioral, cellular and molecular levels.
These characteristics put O. degus in a singular position as a natural rodent model for research into AD pathogenesis and
therapeutics against AD.
