Browsing by Author "Cogram, Patricia"
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Item Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease(2022) Hurley, Michael; Urra, Claudio; Garduno, Maximiliano; Bruno, Agostino; Kimbell, Allison; Wilkinson, Brent; Marino, Cristina; Ezquer, Marcelo; Ezquer, Fernando; Aburto, Pedro; Poulin, Elie; Vasquez, Rodrigo; Deacon, Robert; Avila, Ariel; Altimiras, Francisco; Whitney, Peter; Zampieri, Guido; Angione, Claudio; Constantino, Gabriele; Holmes, Todd; Coba, Marcelo; Xu, Xiangmin; Cogram, PatriciaThe degu (Octodon degus) is a diurnal long-lived rodent that can spontaneously develop molecular and behavioral changes that mirror those seen in human aging. With age some degu, but not all individuals, develop cognitive decline and brain pathology like that observed in Alzheimer’s disease including neuroinflammation, hyperphosphorylated tau and amyloid plaques, together with other co-morbidities associated with aging such as macular degeneration, cataracts, alterations in circadian rhythm, diabetes and atherosclerosis. Here we report the whole-genome sequencing and analysis of the degu genome, which revealed unique features and molecular adaptations consistent with aging and Alzheimer’s disease. We identified single nucleotide polymorphisms in genes associated with Alzheimer’s disease including a novel apolipoprotein E (Apoe) gene variant that correlated with an increase in amyloid plaques in brain and modified the in silico predicted degu APOE protein structure and functionality. The reported genome of an unconventional long-lived animal model of aging and Alzheimer’s disease offers the opportunity for understanding molecular pathways involved in aging and should help advance biomedical research into treatments for Alzheimer’s diseaseItem Spatial maps and oscillations in the healthy hippocampus of Octodon degus, a natural model of sporadic Alzheimer’s disease(2022) Mugnaini, Matias; Polania, Diana; Ezquer, Marcelo; Ezquer, Fernando; Deacon, Robert; Cogram, Patricia; Kropff, EmilioThe Octodon degus is a South American rodent that is receiving increased attention as a potential model of aging and sporadic late-onset Alzheimer’s disease (AD). Impairments in spatial memory tasks in Octodon degus have been reported in relation to either advanced AD-like disease or hippocampal lesion, opening the way to investigate how the function of hippocampal networks affects behavior across AD stages. However, no characterization of hippocampal electrophysiology exists in this species. Here we describe in young, healthy specimens the activity of neurons and local field potential rhythms during spatial navigation tasks with and without objects. Our findings show similarities between the Octodon degus and laboratory rodents. First, place cells with characteristics similar to those found in rats and mice exist in the CA1 subfield of the Octodon degus. Second, the introduction of objects elicits novelty-related exploration and an increase in activity of CA1 cells, with location specific and unspecific components. Third, oscillations of the local field potential are organized according to their spectral content into bands similar to those found in laboratory rodents. These results suggest a common framework of underlying mechanisms, opening the way to future studies of hippocampal dysfunction in this species associated to aging and disease.