Insights into the Gut Microbiome of the South American Leaf-Toed Gecko (Phylodactylus gerropygus) Inhabiting the Core of the Atacama Desert.

Living in arid environments presents unique challenges to organisms, including limited food and water, extreme temperatures, and UV exposure. Reptiles, such as the South American leaf-toed gecko (Phyllodactylus gerrhopygus), have evolved remarkable adaptations to thrive in such harsh conditions. The gut microbiome plays a critical role in host adaptation and health, yet its composition remains poorly characterized in desert reptiles. This study aimed to characterize the composition and abundance of the gut microbiome in P. gerrhopygus inhabiting the hyperarid Atacama Desert, taking into account potential sex differences. Fecal samples from adult female and male geckos were analyzed by 16S rRNA gene amplicon sequencing. No significant differences in bacterial alpha diversity were observed between the sexes. However, the phylum Bacteroidota was more abundant in females, while males had a higher Firmicutes/Bacteroidota ratio. The core microbiome was dominated by the phyla Bacteroidota, Firmicutes, and Proteobacteria in both sexes. Analysis of bacterial composition revealed 481 amplicon sequence variants (ASVs) shared by female and male geckos. In addition, 108 unique ASVs were exclusive to females, while 244 ASVs were unique to males. Although the overall bacterial composition did not differ significantly between the sexes, certain taxa exhibited higher relative abundances in each sex group. This study provides insight into the taxonomic structure of the gut microbiome in a desert-adapted reptile and highlights potential sex-specific differences. Understanding these microbial communities is critical for elucidating the mechanisms underlying host resilience in Earth's most arid environments, and for informing conservation efforts in the face of ongoing climate change.

Impact of prolonged chronic social isolation stress on behavior and multifractal complexity of metabolic rate in Octodon degus.

Social interaction can improve animal performance through the prevention of stress-related events, the provision of security, and the enhancement of reproductive output and survival. We investigated the effects of prolonged chronic social isolation stress on behavioral, cognitive, and physiological performance in the social, long-lived rodent Octodon degus. Degu pups were separated into two social stress treatments: control (CTRL) and chronically isolated (CI) individuals from post-natal and post-weaning until adulthood. We quantified anxiety-like behavior and cognitive performance with a battery of behavioral tests. Additionally, we measured their basal metabolic rate (BMR) and analyzed the multifractal properties of the oxygen consumption time series using Multifractal Detrended Fluctuation Analysis, a well-known method for assessing the fractal characteristics of biological signals. Our results showed that CI induced a significant increase in anxiety-like behaviors and led to a reduction in social and working memory in male degus. In addition, CI-treated degus reduced the multifractal complexity of BMR compared to CTRL, which implies a decrease in the ability to respond to environmental stressors and, as a result, an unhealthy state. In contrast, we did not observe significant effects of social stress on BMR. Multivariate analyses showed a clear separation of behavior and physiological variables into two clusters, corresponding to CI and CTRL degus. This study provides novel insights into the effects of prolonged chronic social isolation stress on behavior, cognitive performance, and metabolic complexity in this rodent animal model. To the best of our knowledge, it is the first study to integrate cognitive-behavioral performance and multifractal dynamics of a physiological signal in response to prolonged social isolation. These findings highlight the importance of social interactions for the well-being and overall performance of social animals.

Long-term social isolation stress exacerbates sex-specific neurodegeneration markers in a natural model of Alzheimer's disease.

Social interactions have a significant impact on health in humans and animal models. Social isolation initiates a cascade of stress-related physiological disorders and stands as a significant risk factor for a wide spectrum of morbidity and mortality. Indeed, social isolation stress (SIS) is indicative of cognitive decline and risk to neurodegenerative conditions, including Alzheimer's disease (AD). This study aimed to evaluate the impact of chronic, long-term SIS on the propensity to develop hallmarks of AD in young degus (Octodon degus), a long-lived animal model that mimics sporadic AD naturally. We examined inflammatory factors, bioenergetic status, reactive oxygen species (ROS), oxidative stress, antioxidants, abnormal proteins, tau protein, and amyloid-ß (Aß) levels in the hippocampus of female and male degus that were socially isolated from post-natal and post-weaning until adulthood. Additionally, we explored the effect of re-socialization following chronic isolation on these protein profiles. Our results showed that SIS promotes a pro-inflammatory scenario more severe in males, a response that was partially mitigated by a period of re-socialization. In addition, ATP levels, ROS, and markers of oxidative stress are severely affected in female degus, where a period of re-socialization fails to restore them as it does in males. In females, these effects might be linked to antioxidant enzymes like catalase, which experience a decline across all SIS treatments without recovery during re-socialization. Although in males, a previous enzyme in antioxidant pathway diminishes in all treatments, catalase rebounds during re-socialization. Notably, males have less mature neurons after chronic isolation, whereas phosphorylated tau and all detectable forms of Aß increased in both sexes, persisting even post re-socialization. Collectively, these findings suggest that long-term SIS may render males more susceptible to inflammatory states, while females are predisposed to oxidative states. In both scenarios, the accumulation of tau and Aß proteins increase the individual susceptibility to early-onset neurodegenerative conditions such as AD.

Age-Dependent Behavioral and Synaptic Dysfunction Impairment Are Improved with Long-Term Andrographolide Administration in Long-Lived Female Degus (Octodon degus).

In Octodon degus, the aging process is not equivalent between sexes and worsens for females. To determine the beginning of detrimental features in females and the ways in which to improve them, we compared adult females (36 months old) and aged females (72 months old) treated with Andrographolide (ANDRO), the primary ingredient in Andrographis paniculata. Our behavioral data demonstrated that age does not affect recognition memory and preference for novel experiences, but ANDRO increases these at both ages. Sociability was also not affected by age; however, social recognition and long-term memory were lower in the aged females than adults but were restored with ANDRO. The synaptic physiology data from brain slices showed that adults have more basal synaptic efficiency than aged degus; however, ANDRO reduced basal activity in adults, while it increased long-term potentiation (LTP). Instead, ANDRO increased the basal synaptic activity and LTP in aged females. Age-dependent changes were also observed in synaptic proteins, where aged females have higher synaptotagmin (SYT) and lower postsynaptic density protein-95 (PSD95) levels than adults. ANDRO increased the N-methyl D-aspartate receptor subtype 2B (NR2B) at both ages and the PSD95 and Homer1 only in the aged. Thus, females exposed to long-term ANDRO administration show improved complex behaviors related to age-detrimental effects, modulating mechanisms of synaptic transmission, and proteins.

Differential Role of Sex and Age in the Synaptic Transmission of Degus (Octodon degus).

Octodon degus are a diurnal long-lived social animal widely used to perform longitudinal studies and complex cognitive tasks to test for physiological conditions with similitude in human behavior. They show a complex social organization feasible to be studied under different conditions and ages. Several aspects in degus physiology demonstrated that these animals are susceptible to environmental conditions, such as stress, fear, feeding quality, and isolation. However, the relevance of these factors in life of this animal depends on sex and age. Despite its significance, there are few studies with the intent to characterize neurological parameters that include these two parameters. To determine the basal neurophysiological status, we analyzed basic electrophysiological parameters generated during basal activity or synaptic plasticity in the brain slices of young and aged female and male degus. We studied the hippocampal circuit of animals kept in social ambient in captivity under controlled conditions. The study of basal synaptic activity in young animals (12-24 months old) was similar between sexes, but female degus showed more efficient synaptic transmission than male degus. We found the opposite in aged animals (60-84 months old), where male degus had a more efficient basal transmission and facilitation index than female degus. Furthermore, female and male degus develop significant but not different long-term synaptic plasticity (LTP). However, aged female degus need to recruit twice as many axons to evoke the same postsynaptic activity as male degus and four times more when compared to young female degus. These data suggest that, unlike male degus, the neural status of aged female degus change, showing less number or functional axons available at advanced ages. Our data represent the first approach to incorporate the effect of sex along with age progression in basal neural status.

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

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.

"Live together, die alone": The effect of re-socialization on behavioural performance and social-affective brain-related proteins after a long-term chronic social isolation stress.

Loneliness affects group-living mammals triggering a cascade of stress-dependent physiological disorders. Indeed, social isolation stress is a major risk factor for several neuropsychiatric disorders including anxiety and depression. Furthermore, social isolation has a negative impact on health and fitness. However, the neurobiological consequences of long-term chronic social isolation stress (LTCSIS) manifested during the adulthood of affected individuals are not fully understood. Our study assessed the impact of LTCSIS and social buffering (re-socialization) on the behavioural performance and social-affective brain-related proteins in diurnal, social, and long-lived Octodon degus (degus). Thereby, anxiety-like and social behaviour, and social recognition memory were assessed in male and female animals subjected to a variety of stress-inducing treatments applied from post-natal and post-weaning until their adulthood. Additionally, we evaluated the relationship among LTCSIS, Oxytocin levels (OXT), and OXT-Ca2+-signalling proteins in the hypothalamus, the hippocampus, and the prefrontal cortex. Our findings suggest that LTCSIS induces anxiety like-behaviour and impairs social novelty preference whereas sociability is unaffected. On the other hand, re-socialization can revert both isolation-induced anxiety and social memory impairment. However, OXT and its signalling remained reduced in the abovementioned brain areas, suggesting that the observed changes in OXT-Ca2+ pathway proteins were permanent in male and female degus. Based on these findings, we conclude degus experience social stress differently, suggesting the existence of sex-related mechanisms to cope with specific adaptive challenges.

Effects of long-lasting social isolation and re-socialization on cognitive performance and brain activity: a longitudinal study in Octodon degus.

Social isolation is considered a stressful situation that results in increased physiological reactivity to novel stimuli, altered behaviour, and impaired brain function. Here, we investigated the effects of long-term social isolation on working memory, spatial learning/memory, hippocampal synaptic transmission, and synaptic proteins in the brain of adult female and male Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects, makes it a unique animal model that can be highly applicable for further social, emotional, cognitive, and aging studies. These animals were socially isolated from post-natal and post-weaning until adulthood. We also evaluated if re-socialization would be able to compensate for reactive stress responses in chronically stressed animals. We showed that long-term social isolation impaired the HPA axis negative feedback loop, which can be related to cognitive deficits observed in chronically stressed animals. Notably, re-socialization restored it. In addition, we measured physiological aspects of synaptic transmission, where chronically stressed males showed more efficient transmission but deficient plasticity, as the reverse was true on females. Finally, we analysed synaptic and canonical Wnt signalling proteins in the hypothalamus, hippocampus, and prefrontal cortex, finding both sex- and brain structure-dependent modulation, including transient and permanent changes dependent on stress treatment.

Andrographolide Reduces Neuroinflammation and Oxidative Stress in Aged Octodon degus.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder in which superior brain functions, such as memory and cognition, are impaired. Currently, no effective treatment is available for AD. Although andrographolide (ANDRO), a compound extracted from the herb Andrographis paniculata, has shown interesting effects in models of several diseases, including AD, its effects on other molecular changes observed in AD, such as neuroinflammation and oxidative stress, have not yet been studied. To evaluate the impact of ANDRO-based intervention on the levels of amyloid-ß (Aß) and neuroinflammatory and oxidative stress markers in the brains of aged Octodon degus, a Chilean rodent, fifty-six-month-old O. degus were treated intraperitoneally with 2 or 4 mg/kg ANDRO. Vehicle-injected and 12-month-old O. degus were used as positive controls. Then, the protein levels of selected markers were assessed via immunohistochemistry and immunoblotting. ANDRO significantly reduced the total Aß burden as well as astrogliosis and interleukin-6 levels. Moreover, ANDRO significantly reduced the levels of 4-hydroxynonenal and N-tyrosine adducts, suggesting a relevant reduction in oxidative stress within aged O. degus brain. Considering that O. degus has been proposed as a potential "natural" model for sporadic AD due to the development of neuropathological markers that resemble this pathology, our results suggest that ANDRO should be further studied to establish its potential as a therapeutic drug for AD.

Ecoimmunology in degus: interplay among diet, immune response, and oxidative stress.

The relationships between immunity, oxidative stress, and diet have not often been studied together. Despite this, it has been shown that dietary proteins can have effects on the functioning of the immune system and the oxidative status of animals. Here we evaluated the effects of dietary proteins on the response to an antigen and oxidative status of Octodon degus (Rodentia). We acclimated adult individuals to high-protein and low-protein diets and evaluated several aspects of the acute phase response and variables associated with oxidative status. After the immune challenge, animals acclimated to the high-protein diet had more inflammatory proteins and body mass losses than the group acclimated to a low-protein diet. Overall, the immune challenge increased the production of inflammatory proteins, total antioxidant capacity, lipid peroxidation, and duration of rest periods. In contrast, we did not find an interaction between diet and the challenge with the antigen. Overall, our results do not reveal an enhanced response to an antigen nor effects on the oxidative status of degus individuals subjected to a high-protein diet.

New Insights into the Spontaneous Human Alzheimer's Disease-Like Model Octodon degus: Unraveling Amyloid-ß Peptide Aggregation and Age-Related Amyloid Pathology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Despite advances in our understanding of the molecular milieu driving AD pathophysiology, no effective therapy is currently available. Moreover, various clinical trials have continued to fail, suggesting that our approach to AD must be revised. Accordingly, the development and validation of new models are highly desirable. Over the last decade, we have been working with Octodon degus (degu), a Chilean rodent, which spontaneously develops AD-like neuropathology, including increased amyloid-ß (Aß) aggregates, tau hyperphosphorylation, and postsynaptic dysfunction. However, for proper validation of degu as an AD model, the aggregation properties of its Aß peptide must be analyzed. Thus, in this study, we examined the capacity of the degu Aß peptide to aggregate in vitro. Then, we analyzed the age-dependent variation in soluble Aß levels in the hippocampus and cortex of third- to fifth-generation captive-born degu. We also assessed the appearance and spatial distribution of amyloid plaques in O. degus and compared them with the plaques in two AD transgenic mouse models. In agreement with our previous studies, degu Aß was able to aggregate, forming fibrillar species in vitro. Furthermore, amyloid plaques appeared in the anterior brain structures of O. degus at approximately 32 months of age and in the whole brain at 56 months, along with concomitant increases in Aß levels and the Aß42/Aß40 ratio, indicating that O. degus spontaneously develops AD-like pathology earlier than other spontaneous models. Based on these results, we can confirm that O. degus constitutes a valuable model to improve AD research.

Long-Term, Fructose-Induced Metabolic Syndrome-Like Condition Is Associated with Higher Metabolism, Reduced Synaptic Plasticity and Cognitive Impairment in Octodon degus.

There has been a progressive increase in the incidence of fructose-induced metabolic disorders, such as metabolic syndrome (MetS). Moreover, novel evidence reported negative effects of high-fructose diets in brain function. This study was designed to evaluate for the first time the effects of long-term fructose consumption (LT-FC) on the normal ageing process in a long-lived animal model rodent, Octodon degus or degu. Moreover, we could replicate human sugar consumption behaviour over time, leading us to understand then the possible mechanisms by which this MetS-like condition could affect cognitive abilities. Our results support that 28 months (from pup to adulthood) of a 15% solution of fructose induced clinical conditions similar to MetS which includes an insulin-resistance scenario together with elevated basal metabolic rate and non-alcoholic fatty liver disease. Additionally, we extended our analysis to evaluate the impact of this MetS-like condition on the functional and cognitive brain processes. Behavioural test suggests that fructose-induced MetS-like condition impair hippocampal-dependent and independent memory performance. Moreover, we also reported several neuropathological events as impaired hippocampal redox balance, together with synaptic protein loss. These changes might be responsible for the alterations in synaptic plasticity and transmitter release observed in these cognitively impaired animals. Our results indicate that LT-FC induced several facets of MetS that eventually could trigger brain disorders, in particular, synaptic dysfunction and reduced cognition.

Andrographolide recovers cognitive impairment in a natural model of Alzheimer's disease (Octodon degus).

The social species Octodon degus (degu) is the only wild-type South American rodent that develops Alzheimer's-like pathology with age. Here, we evaluated the ability of a natural product (Andrographolide, ANDRO), a diterpene of the labdane family obtained from the Asian plant Andrographis paniculata, to recover the cognitive decline in this long-lived animal model. We administered ANDRO to aged degus (56-month old) for 3 months. In addition, in 2 control groups (young degus: 12-month old and aged degus: 56-month old), we administrated saline solution as a vehicle. We evaluated cognitive performance through several behavioral tests. We also performed a series of physiological and biochemical analyses (e.g., electrophysiological and immunoblotting assessment) to identify possible mechanisms underlying cognitive performance associated with age. Our results suggest that there is an effect of aging on the loss of cognitive function, and this decrease in cognitive function was also related to a decrease in the synaptic functions and an increase in the main hallmarks of Alzheimer's disease (AD). More importantly, ANDRO treatments showed the following beneficial effects: (1) recovery of spatial memory and learning performance; (2) recovery of synaptic basal transmission; (3) partial or complete protection of certain synaptic proteins; and (4) a specific neuroprotective effect, including the reduction of phosphorylated tau protein and amyloid beta aggregate maturation in aged degus. Taken together, our results suggest that ANDRO could be used as a potential therapy for AD and support the use of O. degus as a natural model in which to study both neural damage associated with aging processes and the behavioral and neuropathological hallmarks of aging-related diseases such as AD.

On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae).

Cognitive ecologist posits that the more efficiently an animal uses information from the biotic and abiotic environment, the more adaptive are its cognitive abilities. Nevertheless, this approach does not test for natural neurodegenerative processes under field or experimental conditions, which may recover animals information processing and decision making and may explain, mechanistically, maladaptive behaviors. Here, we call for integrative approaches to explain the relationship between ultimate and proximate mechanisms behind social behavior. We highlight the importance of using the endemic caviomorph rodent Octodon degus as a valuable natural model for mechanistic studies of social behavior and to explain how physical environments can shape social experiences that might influence impaired cognitive abilities and the onset and progression of neurodegenerative disorders such as Alzheimer disease. We consequently suggest neuroecological approaches to examine how key elements of the environment may affect neural and cognitive mechanisms associated with learning, memory processes and brain structures involved in social behavior. We propose the following three core objectives of a program comprising interdisciplinary research in O. degus, namely: (1) to determine whether diet types provided after weaning can lead to cognitive impairment associated with spatial memory, learning and predisposing to develop Alzheimer disease in younger ages; (2) to examine if early life social experience has long term effects on behavior and cognitive responses and risk for development Alzheimer disease in later life and (3) To determine if an increase of social interactions in adult degu reared in different degree of social stressful conditions alter their behavior and cognitive responses.

On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae)

Cognitive ecologist posits that the more efficiently an animal uses information from the biotic and abiotic environment, the more adaptive are its cognitive abilities. Nevertheless, this approach does not test for natural neurodegenerative processes under field or experimental conditions, which may recover animals information processing and decision making and may explain, mechanistically, maladaptive behaviors. Here, we call for integrative approaches to explain the relationship between ultimate and proximate mechanisms behind social behavior. We highlight the importance of using the endemic caviomorph rodent Octodon degus as a valuable natural model for mechanistic studies of social behavior and to explain how physical environments can shape social experiences that might influence impaired cognitive abilities and the onset and progression of neurodegenerative disorders such as Alzheimer disease. We consequently suggest neuroecological approaches to examine how key elements of the environment may affect neural and cognitive mechanisms associated with learning, memory processes and brain structures involved in social behavior. We propose the following three core objectives of a program comprising interdisciplinary research in O. degus, namely: (1) to determine whether diet types provided after weaning can lead to cognitive impairment associated with spatial memory, learning and predisposing to develop Alzheimer disease in younger ages; (2) to examine if early life social experience has long term effects on behavior and cognitive responses and risk for development Alzheimer disease in later life and (3) To determine if an increase of social interactions in adult degu reared in different degree of social stressful conditions alter their behavior and cognitive responses.

Age Progression of Neuropathological Markers in the Brain of the Chilean Rodent Octodon degus, a Natural Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the leading cause of age-related dementia worldwide. Several models for AD have been developed to provide information regarding the initial changes that lead to degeneration. Transgenic mouse models recapitulate many, but not all, of the features of AD, most likely because of the high complexity of the pathology. In this context, the validation of a wild-type animal model of AD that mimics the neuropathological and behavioral abnormalities is necessary. In previous studies, we have reported that the Chilean rodent Octodon degus could represent a natural model for AD. In the present work, we further describe the age-related neurodegeneration observed in the O. degus brain. We report some histopathological markers associated with the onset progression of AD, such as glial activation, increase in oxidative stress markers, neuronal apoptosis and the expression of the peroxisome proliferative-activated receptor γ coactivator-1α (PGC-1α). With these results, we suggest that the O. degus could represent a new model for AD research and a powerful tool in the search for therapeutic strategies against AD.

Direct fitness of group living mammals varies with breeding strategy, climate and fitness estimates.

1. Understanding how variation in fitness relates to variation in group living remains critical to determine whether this major aspect of social behaviour is currently adaptive. 2. Available evidence in social mammals aimed to examine this issue remains controversial. Studies show positive (i.e. potentially adaptive), neutral or even negative fitness effects of group living. 3. Attempts to explain this variation rely on intrinsic and extrinsic factors to social groups. Thus, relatively more positive fitness effects are predicted in singularly breeding as opposed to plural breeding species. Fitness effects of sociality in turn may depend on ecological conditions (i.e. extrinsic factors) that influence associated benefits and costs. 4. We used meta-analytic tools to review how breeding strategy or ecological conditions influence the effect size associated with direct fitness-sociality relationships reported in the mammalian literature. Additionally, we determined how taxonomic affiliation of species studied, different fitness and sociality measures used, and major climatic conditions of study sites explained any variation in direct fitness effect size. 5. We found group living had modest, yet positive effects on direct fitness. This generally adaptive scenario was contingent not only upon breeding strategy and climate of study sites, but also on fitness measures examined. Thus, positive and significant effects characterized singular as opposed to plural breeding strategies. 6. We found more positive fitness effects on studies conducted in tropical as opposed to temperate or arid climates. More positive and significant effects were noted on studies that relied on group fecundity, male fecundity and offspring survival as measures of fitness. 7. To conclude, direct fitness consequences of mammalian group living are driven by interspecific differences in breeding strategy and climate conditions. Other factors not examined in this study, namely individual variation in direct and indirect fitness benefits and potential interactions between social and ecological conditions, may be important and require further studies.