Natural AD-Like Neuropathology in Octodon degus: Impaired Burrowing and Neuroinflammation

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, Patricia Cogram.

Journal Name: Current Alzheimer Research

Volume 12 , Issue 4 , 2015

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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.

Keywords: Alzheimer’s disease, beta-amyloid, burrowing, complement, cytokines, Octodon degus.

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Article Details

VOLUME: 12
ISSUE: 4
Year: 2015
Page: [314 - 322]
Pages: 9
DOI: 10.2174/1567205012666150324181652
Price: $58

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