The cognitively impaired degu is a natural animal model well suited for Alzheimer’s disease research

Led by researchers at the University of California, Irvine, a new study reveals that a long-lived Chilean rodent called Degu Degus (degu), is a useful and practical model of natural sporadic Alzheimer’s disease. The results were published today in Acta Neuropathologica Communications.

“We found robust neurodegenerative features in older degus with cognitive impairment, including hippocampal neuronal loss, altered parvalbumin and perineuronal network staining in the cortex, and increased c-Fos neuronal activation. in the cortex that is consistent with neural circuit hyperactivity that are commonly reported in human patients with Alzheimer’s disease,” explained corresponding author Xiangmin Xu, PhD, Professor and Chancellor’s Fellow in Anatomy and Neurobiology at the UCI School of Medicine and director of the Center for Neural Circuit Mapping. “By focusing on a subset of older degus who exhibit AD-like behavioral deficits and correlative neuropathology, we establish outbred degus as a natural model of sporadic Alzheimer’s disease and demonstrate the potential importance of past history wild-type outbred genetics for the pathogenesis of Alzheimer’s disease.”

This study was motivated by the need to settle previous debates regarding whether the degus may be a useful natural model of AD. There is a critical need for natural, non-murine animal models for Alzheimer’s disease research, as particularly highlighted by the NIH RFA “Novel/Unconventional Animal Models of Alzheimer’s Disease” . The handful of published papers on degus with different genetic backgrounds yield inconsistent results on sporadic AD-like pathological features, with notably different results between laboratory inbred degus and outbred degus.

“We suspect that inconsistent results between different studies may be due to comparison of neuropathology results of inbred colonies in the laboratory versus more genetically diverse outbred degus, relatively low statistical power for the sample size and to the lack of behavioral screening,” Xu said.

This study revealed that aged, inbred degus possessing both behavioral and neuropathological characteristics that resemble human AD pathologies, have clear advantages over common rodent models (mice and rats) for the study of AD. MY. Furthermore, a portion of the outbred degu population naturally develops additional conditions similar to type 2 diabetes, macular degeneration, and atherosclerosis with age, providing a means to study the comorbidities of degu. Alzheimer’s disease in the degu.

“Our results, taken together, show spontaneous correlative AD-like phenotypes in cognitive performance and neuropathology in aged, outbred degus. This confirms that aged degus are a useful and practical model of natural sporadic AD,” Xu said.

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

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease characterized by irreversible cognitive decline and specific pathological lesions in the brain that significantly alter the lives of people with the disease. There are approximately 44 million people with Alzheimer’s disease worldwide, with more than 90% of these cases being late onset and occurring sporadically.

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