Cognitively impaired aged Octodon degus recapitulate major neuropathological features of sporadic Alzheimer's disease.

The long-lived Chilean rodent (Octodon degus) has been reported to show spontaneous age-dependent neuropathology and cognitive impairments similar to those observed in human AD. However, the handful of published papers on degus of differing genetic backgrounds yield inconsistent findings about sporadic AD-like pathological features, with notably differing results between lab in-bred degus versus outbred degus. This motivates more extensive characterization of spontaneously occurring AD-like pathology and behavior in degus. In the present study, we show AD-like neuropathological markers in the form of amyloid deposits and tau abnormalities in a cognitively impaired subset of aged outbred degus. Compared to the aged degus that show normal burrowing behavior, the age-matched degus with burrowing behavior deficits correlatively exhibit detectable human AD-like Aß deposits and tau neuropathology, along with neuroinflammatory markers that include enhanced microglial activation and higher numbers of reactive astrocytes in the brain. This subset of cognitively impaired aged degus also exhibits cerebral amyloid angiopathy and tauopathy. We find robust neurodegenerative features in behaviorally deficient aged degus, including hippocampal neuronal loss, altered parvalbumin and perineuronal net staining in the cortex, and increased c-Fos neuronal activation in the cortex that is consistent with the neural circuit hyperactivity reported in human AD patients. By focusing on the subset of aged degus that show AD-like behavioral deficits and correlative neuropathology, our findings establish outbred degus as a natural model of sporadic AD and demonstrate the potential importance of wild-type outbred genetic backgrounds for AD pathogenesis.

Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease.

The 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 disease.

A Technical Note of Improvement of the Elnady Technique for Tissue Preservation in Veterinary Anatomy.

Teaching veterinary anatomy has been subjected to changes and restrictions that have promoted the development of new techniques for preserving organs and cadavers. The Elnady technique is a recent method for the conservation of tissues. Specimens produced with this technique are realistic, durable, soft, and flexible, but an undesirable feature is the discoloration of tissues. In the present study, we describe modifications of the Elnady technique for organ and tissue preservation. Specimens were prepared on the theoretical basis of the Elnady technique, but at low temperatures and with longer durations for the fixation, dehydration, glycerin impregnation and curing processes. Furthermore, the tissues were pigmented with a red vegetable pigment before dehydration or in the glycerin impregnation process. The results show high-quality specimens with minimal shrinkage and natural color aspects. The modified Elnady technique is adequate for producing specimens of better contrast for education purposes.

Can social behaviour drive accessory olfactory bulb asymmetries? Sister species of caviomorph rodents as a case in point.

In mammals, the accessory olfactory or vomeronasal system exhibits a wide variety of anatomical arrangements. In caviomorph rodents, the accessory olfactory bulb (AOB) exhibits a dichotomic conformation, in which two subdomains, the anterior (aAOB) and the posterior (pAOB), can be readily distinguished. Interestingly, different species of this group exhibit bias of different sign between the AOB subdomains (aAOB larger than pAOB or vice versa). Such species-specific biases have been related with contrasting differences in the habitat of the different species (e.g. arid vs. humid environments). Aiming to deepen these observations, we performed a morphometric comparison of the AOB subdomains between two sister species of octodontid rodents, Octodon lunatus and Octodon degus. These species are interesting for comparative purposes, as they inhabit similar landscapes but exhibit contrasting social habits. Previous reports have shown that O. degus, a highly social species, exhibits a greatly asymmetric AOB, in which the aAOB has twice the size of the pAOB and features more and larger glomeruli in its glomerular layer (GL). We found that the same as in O. degus, the far less social O. lunatus also exhibits a bias, albeit less pronounced, to a larger aAOB. In both species, this bias was also evident for the mitral/tufted cells number. But unlike in O. degus, in O. lunatus this bias was not present at the GL. In comparison with O. degus, in O. lunatus the aAOB GL was significantly reduced in volume, while the pAOB GL displayed a similar volume. We conclude that these sister species exhibit a very sharp difference in the anatomical conformation of the AOB, namely, the relative size of the GL of the aAOB subdomain, which is larger in O. degus than in O. lunatus. We discuss these results in the context of the differences in the lifestyle of these species, highlighting the differences in social behaviour as a possible factor driving to distinct AOB morphometries.

Anatomical Specializations Related to Foraging in the Visual System of a Nocturnal Insectivorous Bird, the Band-Winged Nightjar (Aves: Caprimulgiformes).

Nocturnal animals that rely on their visual system for foraging, mating, and navigation usually exhibit specific traits associated with living in scotopic conditions. Most nocturnal birds have several visual specializations, such as enlarged eyes and an increased orbital convergence. However, the actual role of binocular vision in nocturnal foraging is still debated. Nightjars (Aves: Caprimulgidae) are predators that actively pursue and capture flying insects in crepuscular and nocturnal environments, mainly using a conspicuous "sit-and-wait" tactic on which pursuit begins with an insect flying over the bird that sits on the ground. In this study, we describe the visual system of the band-winged nightjar (Systellura longirostris), with emphasis on anatomical features previously described as relevant for nocturnal birds. Orbit convergence, determined by 3D scanning of the skull, was 73.28°. The visual field, determined by ophthalmoscopic reflex, exhibits an area of maximum binocular overlap of 42°, and it is dorsally oriented. The eyes showed a nocturnal-like normalized corneal aperture/axial length index. Retinal ganglion cells (RGCs) were relatively scant, and distributed in an unusual oblique-band pattern, with higher concentrations in the ventrotemporal quadrant. Together, these results indicate that the band-winged nightjar exhibits a retinal specialization associated with the binocular area of their dorsal visual field, a relevant area for pursuit triggering and prey attacks. The RGC distribution observed is unusual among birds, but similar to that of some visually dependent insectivorous bats, suggesting that those features might be convergent in relation to feeding strategies.

Effects of Habitat and Social Complexity on Brain Size, Brain Asymmetry and Dentate Gyrus Morphology in Two Octodontid Rodents.

Navigational and social challenges due to habitat conditions and sociality are known to influence dentate gyrus (DG) morphology, yet the relative importance of these factors remains unclear. Thus, we studied three natural populations of O. lunatus (Los Molles) and Octodon degus (El Salitre and Rinconada), two caviomorph species that differ in the extent of sociality and with contrasting vegetation cover of habitat used. The brains and DG of male and female breeding degus with simultaneous information on their physical and social environments were examined. The extent of sociality was quantified from total group size and range area overlap. O. degus at El Salitre was more social than at Rinconada and than O. lunatus from Los Molles. The use of transects to quantify cover of vegetation (and other physical objects in the habitat) and measures of the spatial behavior of animals indicated animal navigation based on unique cues or global landmarks is more cognitively challenging to O. lunatus. During lactation, female O. lunatus had larger brains than males. Relative DG volume was similar across sexes and populations. The right hemisphere of male and female O. lunatus had more cells than the left hemisphere, with DG directional asymmetry not found in O. degus. Degu population differences in brain size and DG cell number seemed more responsive to differences in habitat than to differences in sociality. Yet, large-sized O. degus (but not O. lunatus) that ranged over larger areas and were members of larger social groups had more DG cells per hemisphere. Thus, within-population variation in DG cell number by hemisphere was consistent with a joint influence of habitat and sociality in O. degus at El Salitre.

Deterioration of the Gαo vomeronasal pathway in sexually dimorphic mammals.

In mammals, social and sexual behaviours are largely mediated by the vomeronasal system (VNS). The accessory olfactory bulb (AOB) is the first synaptic locus of the VNS and ranges from very large in Caviomorph rodents, small in carnivores and ungulates, to its complete absence in apes, elephants, most bats and aquatic species. Two pathways have been described in the VNS of mammals. In mice, vomeronasal neurons expressing Gαi2 protein project to the rostral portion of the AOB and respond mostly to small volatile molecules, whereas neurons expressing Gαo project to the caudal AOB and respond mostly to large non-volatile molecules. However, the Gαo-expressing pathway is absent in several species (horses, dogs, musk shrews, goats and marmosets) but no hypotheses have been proposed to date to explain the loss of that pathway. We noted that the species that lost the Gαo pathway belong to Laurasiatheria and Primates lineages, both clades with ubiquitous sexual dimorphisms across species. To assess whether similar events of Gαo pathway loss could have occurred convergently in dimorphic species we studied G-protein expression in the AOB of two species that independently evolved sexually dimorphic traits: the California ground squirrel Spermophilus beecheyi (Rodentia; Sciurognathi) and the cape hyrax Procavia capensis (Afrotheria; Hyracoidea). We found that both species show uniform expression of Gαi2-protein throughout AOB glomeruli, while Gαo expression is restricted to main olfactory glomeruli only. Our results suggest that the degeneration of the Gαo-expressing vomeronasal pathway has occurred independently at least four times in Eutheria, possibly related to the emergence of sexual dimorphisms and the ability of detecting the gender of conspecifics at distance.