The Cognitively Impaired Degu is a Natural Animal Model Well-suited for Alzheimer’s Research – ScienceDaily

A new study led by researchers from the University of California at Irvine reveals that a long-lived Chilean rodent is named after it. octagonal degus (degu) is a useful and practical model of native sporadic Alzheimer’s Disease. Findings published today Acta Neuropathological Communication.

“We found potent neurodegenerative features in cognitively impaired aged degus, including hippocampal neuronal loss, altered parvalbumin and perineuronal net staining in the cortex, and increased c-Fos neuronal activation consistent with neural circuit hyperactivity commonly reported in the cortex of human Alzheimer’s Disease patients,” he explained. corresponding author Xiangmin Xu, PhD, professor and Chancellor of anatomy and neurobiology and director of the Center for Neural Circuit Mapping at the UCI School of Medicine. “By focusing on a subset of elderly degus that show AD-like behavioral deficits and associated neuropathology, we establish the sequenced degus as a natural model of sporadic AD and demonstrate the potential importance of wild-type genetic backgrounds for AD pathogenesis.”

This study was motivated by the need to resolve previous debates about whether the degus could be a useful natural model of AD. As particularly emphasized by the NIH RFA “Novel/Non-traditional Animal Models of Alzheimer’s Disease,” there is a critical need for non-rodent, natural animal models for Alzheimer’s research. A handful of published papers on degus with different genetic backgrounds give inconsistent findings about sporadic AD-like pathological traits and give significantly different results between lab-grown degus and outside-grown degus.

“We suspect that the inconsistent findings between the different studies may have been due to the comparison of neuropathology results from in-lab-grown colonies with more genetically diverse degus, relatively low statistical power for the sample size, and lack of behavioral screening,” Xu said.

This study revealed that old and aged degus, with both behavioral and neuropathological features resembling human AD pathologies, have clear advantages over common rodent models (mice and rats) for studying AD. Also, some of the next-generation degu population develop additional conditions with age, such as type-2 diabetes, macular degeneration, and atherosclerosis, providing a way to explore AD comorbidities in the degu.

“Added together, our findings show spontaneous AD-like correlated phenotypes in cognitive performance and neuropathology in the elderly, old degus. This supports that the elderly degus is a useful and practical model of natural sporadic AD,” said Xu.

Zhiqun Tan, PhD, associate researcher at UCI CNCM and UCIMIND, and B. Maximiliano Garduño, a graduate student in the UCI Department of Anatomy and Neurobiology, are co-authors of the paper. Other members of the research team include Todd Holmes, PhD, of the UCI School of Medicine’s Division of Physiology and Biophysics; Lujia Chen, a biomedical engineering graduate student at UCI; and international collaborators Patricia Cogram, PhD, associate professor and Pedro Fernández Aburto, PhD, from the Institute of Ecology and Biodiversity, University of Chile. This work was supported by the National Institutes of Health.

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease characterized by irreversible cognitive decline in the brain and specific pathological lesions that greatly impair the lives of individuals suffering from this condition. There are approximately 44 million people worldwide who suffer from AD, and more than 90 percent of these cases occur late-onset and sporadically.

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