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

作者：Deacon Robert M J; Altimiras Francisco J; Bazan Leon Enrique A; Pyarasani Rhada D; Nachtigall Fabiane M; Santos Leonardo S; Tsolaki Anthony G; Pednekar Lina; Kishore Uday; Biekofsky Rodolfo R; Vasquez Rodrigo A; Cogram Patricia^*

来源：Current Alzheimer Research, 2015, 12(4): 314-322.

DOI：10.2174/1567205012666150324181652

• Alzheimer's disease
• beta-amyloid
• burrowing
• complement
• cytokines
• Octodon degus

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-beta (A beta) 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 AD-like 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 stress-related 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.

• 出版日期2015