Lack of spontaneous age-related brain pathology in Octodon degus: a reappraisal of the model

Bourdenx, Mathieu; Doveró, Sandra; Thiolat, Marie-Laure; Bézard, Erwan; Dehay, Benjamin

doi:10.1038/srep45831

Cited by 20 publications

(8 citation statements)

References 24 publications

(65 reference statements)

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“…The degus offer new opportunities to investigate the fundamental question of whether Aβ and tau in the retina are associated with an accelerated aging process. It should also be acknowledged that although the degus have been described as a sporadic AD model with AD-like neuropathology, the occurrence of AD may be variable and not all colonies develop neuropathology in the brain and retina (Steffen et al, 2016;Bourdenx et al, 2017). As an animal model of aging or for AD investigation, it is important to consider the animal colony husbandry that includes exercise, and nutrition as these are important factors that may affect amyloidosis (Van der Auwera et al, 2005;Nichol et al, 2008;Zhao et al, 2015;Prado Lima et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus

et al. 2020

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Accumulation of amyloid-beta (Aβ) peptides is regarded as the hallmark of neurodegenerative alterations in the brain of Alzheimer's disease (AD) patients. In the eye, accumulation of Aβ peptides has also been suggested to be a trigger of retinal neurodegenerative mechanisms. Some pathological aspects associated with Aβ levels in the brain are synaptic dysfunction, neurochemical remodeling and glial activation, but these changes have not been established in the retina of animals with Aβ accumulation. We have employed the Octodon degus in which Aβ peptides accumulated in the brain and retina as a function of age. This current study investigated microglial morphology, expression of PSD95, synaptophysin, Iba-1 and choline acetyltransferase (ChAT) in the retina of juvenile, young and adult degus using immunolabeling methods. Neurotransmitters glutamate and gamma-aminobutyric acid (GABA) were detected using immunogold labeling and glutamate receptor subunits were quantified using Western blotting. There was an age-related increase in presynaptic and a decrease in post-synaptic retinal proteins in the retinal plexiform layers. Immunolabeling showed changes in microglial morphology characteristic of intermediate stages of activation around the optic nerve head (ONH) and decreasing activation toward the peripheral retina. Neurotransmitter expression pattern changed at juvenile ages but was similar in adults. Collectively, the results suggest that microglial activation, synaptic remodeling and neurotransmitter changes may be consequent to, or parallel to Aβ peptide and phosphorylated tau accumulation in the retina.

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Section: Introductionmentioning

confidence: 99%

Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus

et al. 2020

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“…From a genetic point of view, there are high similarities between human and degus proteins, such as ApoE4, amyloid-β peptide, and tau protein (Salazar et al, 2016 ; Steffen et al, 2016 ; Hurley et al, 2018 ). However, two studies questioned the validity of degus as a valuable model for AD research (Bourdenx et al, 2016 ; Steffen et al, 2016 ). A possible explanation for their findings is that the small group of animals per group they used was not assessed for AD-like behavioral changes before the neuropathology analysis was conducted (Hurley et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

A Multivariate Assessment of Age-Related Cognitive Impairment in Octodon degus

Rivera

Lindsay

Oliva

et al. 2021

Front. Integr. Neurosci.

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Aging is a progressive functional decline characterized by a gradual deterioration in physiological function and behavior. The most important age-related change in cognitive function is decline in cognitive performance (i.e., the processing or transformation of information to make decisions that includes speed of processing, working memory, and learning). The purpose of this study is to outline the changes in age-related cognitive performance (i.e., short-term recognition memory and long-term learning and memory) in long-lived Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects makes it a unique animal model for exploring the mechanisms underlying the behavioral and cognitive deficits related to natural aging. In this study, we examined young adult female degus (12- and 24-months-old) and aged female degus (38-, 56-, and 75-months-old) that were exposed to a battery of cognitive-behavioral tests. Multivariate analyses of data from the Social Interaction test or Novel Object/Local Recognition (to measure short-term recognition memory), and the Barnes maze test (to measure long-term learning and memory) revealed a consistent pattern. Young animals formed a separate group of aged degus for both short- and long-term memories. The association between the first component of the principal component analysis (PCA) from short-term memory with the first component of the PCA from long-term memory showed a significant negative correlation. This suggests age-dependent differences in both memories, with the aged degus having higher values of long-term memory ability but poor short-term recognition memory, whereas in the young degus an opposite pattern was found. Approximately 5% of the young and 80% of the aged degus showed an impaired short-term recognition memory; whereas for long-term memory about 32% of the young degus and 57% of the aged degus showed decreased performance on the Barnes maze test. Throughout this study, we outlined age-dependent cognitive performance decline during natural aging in degus. Moreover, we also demonstrated that the use of a multivariate approach let us explore and visualize complex behavioral variables, and identified specific behavioral patterns that allowed us to make powerful conclusions that will facilitate further the study on the biology of aging. In addition, this study could help predict the onset of the aging process based on behavioral performance.

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“…Different authors have shown that these animals naturally accumulate neuropathological proteins, such as β-amyloid deposits and neurofibrillary tangles of phosphorylated tau protein, as well as other signs of neurodegeneration [19,54]. In terms of PD pathology, only one study has been carried out to find characteristic hallmarks, but the authors failed to detect α-synuclein deposits or loss of neuronal density in old specimens of O. degus [55]. However, this discrepancy might be due to the influence of external factors that could favor neuropathological hallmarks, or even the methodology used was not able to detect non-fibrillary aggregates [14].…”

Section: Discussionmentioning

confidence: 99%

A New Tool to Study Parkinsonism in the Context of Aging: MPTP Intoxication in a Natural Model of Multimorbidity

Cuenca‐Bermejo

Pizzichini

Gonçalves

et al. 2021

IJMS

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The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100β were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging.

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Lack of spontaneous age-related brain pathology in Octodon degus: a reappraisal of the model

Cited by 20 publications

References 24 publications

Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus

Evidence of Synaptic and Neurochemical Remodeling in the Retina of Aging Degus

A Multivariate Assessment of Age-Related Cognitive Impairment in Octodon degus

A New Tool to Study Parkinsonism in the Context of Aging: MPTP Intoxication in a Natural Model of Multimorbidity

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