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Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome. C57BL/6 male mice with obesity and metabolic syndrome, continuously fed with an HFD, were exposed to EE. We analyzed the gut microbiota of the mice by sequencing the 16s rRNA gene at different intervals, including on day 0 and 12 and 24 weeks after EE exposure. Fasting glucose levels, glucose tolerance, insulin resistance, food intake, weight gain, lipid profile, hepatic steatosis, and inflammatory mediators were evaluated in serum, adipose tissue, and the colon. We demonstrate that EE intervention prevents the progression of HFD-induced dysbiosis, reducing taxa associated with metabolic syndrome (Tepidimicrobium, Acidaminobacteraceae, and Fusibacter) while promoting those linked to healthy physiology (Syntrophococcus sucrumutans, Dehalobacterium, Prevotella, and Butyricimonas). Furthermore, EE enhances intestinal barrier integrity, increases mucin-producing goblet cell population, and upregulates Muc2 expression in the colon. These alterations correlate with reduced systemic lipopolysaccharide levels and attenuated colon inflammation, resulting in normalized glucose metabolism, diminished adipose tissue inflammation, reduced liver steatosis, improved lipid profiles, and a significant reduction in body weight gain despite mice's continued HFD consumption. Our findings highlight EE as a promising anti-inflammatory strategy for managing obesity-related metabolic dysregulation and suggest its potential in developing probiotics targeting EE-modulated microbial taxa.

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Here, we explored the impact of prolonged environmental enrichment (EE) on behavioral, neurochemical, and epigenetic changes in the serotonin transporter gene in mice subjected to a two-hit schizophrenia model. The methodology involved administering the viral mimetic PolyI:C to neonatal Swiss mice as a first hit during postnatal days (PND) 5-7, or a sterile saline solution as a control. At PND21, mice were randomly assigned either to standard environment (SE) or EE housing conditions. Between PND35-44, the PolyI:C-treated group was submitted to various unpredictable stressors, constituting the second hit. Behavioral assessments were conducted on PND70, immediately after the final EE exposure. Following the completion of behavioral assessments, we evaluated the expression of proteins in the hippocampus that are indicative of microglial activation, such as Iba-1, as well as related to neurogenesis, including doublecortin (Dcx). We also performed methylation analysis on the serotonin transporter gene (Slc6a4) to investigate alterations in serotonin signaling. The findings revealed that EE for 50 days mitigated sensorimotor gating deficits and working memory impairments in two-hit mice and enhanced their locomotor and exploratory behaviors. EE also normalized the overexpression of hippocampal Iba-1 and increased the expression of hippocampal Dcx. Additionally, we observed hippocampal demethylation of the Slc6a4 gene in the EE-exposed two-hit group, indicating epigenetic reprogramming. These results contribute to the growing body of evidence supporting the protective effects of long-term EE in counteracting behavioral disruptions caused by the two-hit schizophrenia model, pointing to enhanced neurogenesis, diminished microglial activation, and epigenetic modifications of serotonergic pathways as underlying mechanisms.

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BACKGROUND: Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor coordination, and decreased muscle tone. However, it is not known whether loss of muscle strength occurs, and which interventions will effectively mitigate physical PAE impairments. We aimed to investigate whether physical alteration persists during adolescence and whether exercise is an effective intervention. RESULTS: Using paradigms to evaluate different physical qualities, we described that early adolescent PAE animals have significant alterations in agility and strength, without alterations in balance and coordination compared to CTRL animals. We evaluated the effectiveness of 3 different exercise protocols for 4 weeks: Enrichment environment (EE), Endurance exercise (EEX), and Resistance exercise (REX). The enriched environment significantly improved the strength in the PAE group but not in the CTRL group whose strength parameters were maintained even during exercise. Resistance exercise showed the greatest benefits in gaining strength, and endurance exercise did not. CONCLUSION: PAE induced a significant decrease in strength compared to CTRL in PND21. Resistance exercise is the most effective to reverse the effects of PAE on muscular strength. Our data suggests that individualized, scheduled, and supervised training of resistance is more beneficial than endurance or enriched environment exercise for adolescents FASD.

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Ethanol (EtOH) intake and noise exposure are particularly concerning among human adolescents because the potential to harm brain. Unfortunately, putative underlying mechanisms remain to be elucidated. Moreover, implementing non-pharmacological strategies, such as enriched environments (EE), would be pertinent in the field of neuroprotection. This study aims to explore possible underlying triggering mechanism of hippocampus-dependent behaviors in adolescent animals of both sexes following ethanol intake, noise exposure, or a combination of both, as well as the impact of EE. Adolescent Wistar rats of both sexes were subjected to an intermittent voluntary EtOH intake paradigm for one week. A subgroup of animals was exposed to white noise for two hours after the last session of EtOH intake. Some animals of both groups were housed in EE cages. Hippocampal-dependent behavioral assessment and hippocampal oxidative state evaluation were performed. Results show that different hippocampal-dependent behavioral alterations might be induced in animals of both sexes after EtOH intake and sequential noise exposure, that in some cases are sex-specific. Moreover, hippocampal oxidative imbalance seems to be one of the potential underlying mechanisms. Additionally, most behavioral and oxidative alterations were prevented by EE. These findings suggest that two frequently found environmental agents may impact behavior and oxidative pathways in both sexes in an animal model. In addition, EE resulted a partially effective neuroprotective strategy. Therefore, it could be suggested that the implementation of a non-pharmacological approach might also potentially provide neuroprotective advantages against other challenges. Finally, considering its potential for translational human benefit might be worth.

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In the literature, there is consistent evidence related to the influence of chewing on brain functions, either from experimental models or in humans. In the case of humans, most results are restricted to functional tests, lacking cellular or molecular evidence. In the described method, the possibility of using experimental models is presented, as well as the mimicry of deprivation and rehabilitation of masticatory activity and without stress impact. By opting for the use of mash feed, instead of extracting or implanting an intraoral device, alternations between restriction and rehabilitation of mastication were imposed on murine models. The animals completed various temporal windows, with aging also representing a potential factor for translational dementia associations. Additionally, animals were segregated into environments characterized as either standard, simulating a sedentary lifestyle, or enriched, rich in sensorimotor and visuospatial stimulation. Thus, it was possible to study the influence of changes in masticatory activity, associated with aging and environmental enrichment, on cells from subregions of the hippocampus, as well as on performance in tests of learning and spatial memory.•Animal model for masticatory activity alteration;•Masticatory deprivation and rehabilitation, and•Models to study the interaction among masticatory activity, aging and enrichment environment.

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Introduction: The present review aimed to systematically summarize the impacts of environmental enrichment (EE) on cerebral oxidative balance in rodents exposed to normal and unfavorable environmental conditions. Methods: In this systematic review, four databases were used: PubMed (830 articles), Scopus (126 articles), Embase (127 articles), and Science Direct (794 articles). Eligibility criteria were applied based on the Population, Intervention, Comparison, Outcomes, and Study (PICOS) strategy to reduce the risk of bias. The searches were carried out by two independent researchers; in case of disagreement, a third participant was requested. After the selection and inclusion of articles, data related to sample characteristics and the EE protocol (time of exposure to EE, number of animals, and size of the environment) were extracted, as well as data related to brain tissues and biomarkers of oxidative balance, including carbonyls, malondialdehyde, nitrotyrosine, oxygen-reactive species, and glutathione (reduced/oxidized). Results: A total of 1,877 articles were found in the four databases, of which 16 studies were included in this systematic review. The results showed that different EE protocols were able to produce a global increase in antioxidant capacity, both enzymatic and non-enzymatic, which are the main factors for the neuroprotective effects in the central nervous system (CNS) subjected to unfavorable conditions. Furthermore, it was possible to notice a slowdown in neural dysfunction associated with oxidative damage, especially in the prefrontal structure in mice. Discussion: In conclusion, EE protocols were determined to be valid tools for improving oxidative balance in the CNS. The global decrease in oxidative stress biomarkers indicates refinement in reactive oxygen species detoxification, triggering an improvement in the antioxidant network.

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Social isolation (SI) is related to adverse neurobehavioral effects and neurochemical changes when it occurs early in development. On the other hand, environmental enrichment (EE) is associated with a reduction in anxiety-like and depression-like behavior, as well as an increase in serotonin (5-HT) levels in the prefrontal cortex and hippocampus in rodents. This study systematically reviewed the effects of SI and EE on emotional behavior and serotonergic system components in rats after weaning. Primary experimental studies that used subgroups of rats subjected to SI, EE, and normal social conditions after weaning were considered eligible. Studies that used transgenic rodents, ex vivo studies, in vitro studies, human research, or in silico studies were ineligible. Two authors completed searches in Medline/PubMed, LILACS, Scopus, Web of Science, EMBASE, and Open Gray. The Kappa index was calculated to assess agreement between reviewers and assess study quality. The results showed that the animals exposed to EE showed better adaptation to a new environment. Furthermore, EE increased 5-HT levels in the hippocampus and prefrontal cortex of rodents. Thus, it appears that an EE during the critical period of development may reduce anxiety/depression-like behaviors, as well as increase long-term neurotransmitter response.

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Environment enrichment (EE) is a well-known eustress model showing beneficial effects in different psychiatric diseases, but its positive properties in panic disorders are not yet established. The confrontation between prey and predator in complex arenas has been validated as a putative panic attack model. The principal aim of this work was to investigate the role of the EE on panic-like defensive responses elicited by mice threatened by venomous snakes. After 6 weeks of exposure either to an enriched or standard environments, 36 male mice were habituated in a complex polygonal arena for snakes containing an artificial burrow and elevated platforms for escape. The animals were confronted by Bothrops jararaca for 5 min, and the following antipredatory responses were recorded: defensive attention, stretched attend posture, flat back approach, prey versus predator interaction, oriented escape behavior, time spent in a safe place, and number of crossings. Mice threatened by snakes displayed several antipredatory reactions as compared to the exploratory behavior of those animals submitted to a nonthreatening situation (toy snake) in the same environment. Notably, EE causes anxiolytic- and panicolytic-like effects significantly decreasing the defensive attention and time spent in safe places and significantly increasing both prey versus predator interaction and exploratory behavior. In conclusion, our data demonstrate that EE can alter the processing of fear modulation regarding both anxiety- and panic-like responses in a dangerous condition, significantly modifying the decision-making defensive strategy.

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Environmental factors such as undernutrition and environmental enrichment can promote changes in the molecular and behavioural mechanisms related to cognition. Herein, we investigated the effect of enriched environment stimulation in rats that were malnourished in the pre- and postnatal periods on changes in the gene expression of brain-derived neurotrophic factor and its receptor in the hippocampus, as well as on anxiety traits and memory. Early undernutrition promoted weight reduction, increased the risk analysis, reduced permanence in the open arm of the elevated plus-maze and induced a reduction in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B. However, exposure to an enriched environment from 30 to 90 days' old maintained the malnourished phenotype, leading to weight reduction in the control group. In addition, the enriched environment did not alter the risk assessment in the undernourished group, but it did increase the frequency of labyrinth entries. Sixty-day exposure to the enriched environment resulted in a reversal in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus of malnourished rats and favoured of long-term memory in the object recognition test in the open-field. These results suggest that an enriched environment may have a protective effect in adult life by inducing changes in long-term memory and anxiety traits in animals that were undernourished in early life. Furthermore, reversing these effects of undernutrition involves mechanisms linked to the molecular signalling of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus.

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This systematic review aims to evaluate the influence of environmental enrichment (EE) on oncological factors in experimental studies involving various types of cancer models. A comprehensive search was conducted in three databases: PubMed (161 articles), Embase (335 articles), and Scopus (274 articles). Eligibility criteria were applied based on the PICOS strategy to minimize bias. Two independent researchers performed the searches, with a third participant resolving any discrepancies. The selected articles were analyzed, and data regarding sample characteristics and EE protocols were extracted. The outcomes focused solely on cancer and tumor-related parameters, including cancer type, description of the cancer model, angiogenesis, tumor occurrence, volume, weight, mice with tumors, and tumor inhibition rate. A total of 770 articles were identified across the three databases, with 12 studies meeting the inclusion criteria for this systematic review. The findings demonstrated that different EE protocols were effective in significantly reducing various aspects of tumor growth and development, such as angiogenesis, volume, weight, and the number of mice with tumors. Furthermore, EE enhanced the rate of tumor inhibition in mouse cancer models. This systematic review qualitatively demonstrates the impacts of EE protocols on multiple parameters associated with tumor growth and development, including angiogenesis, occurrence, volume, weight, and tumor incidence. Moreover, EE demonstrated the potential to increase the rate of tumor inhibition. These findings underscore the importance of EE as a valuable tool in the management of cancer.

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Remembering conspecifics is paramount for the establishment and maintenance of groups. Here we asked whether the variability in social behavior caused by different breeding strategies affects social recognition memory (SRM). We tested the hypothesis that the inbred Swiss and the outbred C57BL/6 mice behave differently on SRM. Social memory in C57BL/6 mice endured at least 14 days, while in Swiss mice lasted 24 h but not ten days. We showed previously that an enriched environment enhanced the persistence of SRM in Swiss mice. Here we reproduced this result and added that it also increases the survival of adult-born neurons in the hippocampus. Next, we tested whether prolonged SRM observed in C57BL/6 mice could be changed by diminishing the trial duration or using an interference stimulus after learning. Neither short acquisition time nor interference during consolidation affected it. However, social isolation impaired SRM in C57BL/6 mice, similar to what was previously observed in Swiss mice. Our results demonstrate that SRM expression can vary according to the mouse strain, which shows the importance of considering this variable when choosing the most suitable model to answer specific questions about this memory system. We also demonstrate the suitability of both C57BL/6 and Swiss strains for exploring the impact of environmental conditions and adult neurogenesis on social memory.

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Environmental enrichment is a widely used experimental manipulation that physically, cognitively and socially stimulates individuals. It has a great variety of long-term effects at neuroanatomical, neurochemical, and behavioral level; however, the influence of parental environmental enrichment during gestation and pregestation on the development of the offspring and on the mother's behavior has been poorly explored. This article presents a review of the literature from the year 2000 about the effects of maternal and paternal environmental enrichment on the behavioral, endocrine, and neural systems of offspring and parents. Relevant research terms were searched for on the biomedical databases, PubMed, Medline, ScienceDirect, and Google Scholar. The data suggest that paternal/maternal environmental enrichment can profoundly affect the developmental trajectories of offspring through putative epigenetic mechanisms. Environmental enrichment presents as a promising therapeutic tool for human health interventions, especially to counteract the deleterious effects of impoverished and adverse growing conditions.

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Anxiety is being increasingly diagnosed in the elderly population. In this sense, epidemiologic data have linked late-life anxiety disorders to increased cognitive decline, morbidity, and even mortality. In addition, studies have already reported the influence of the environment on the association between aging and anxiety. Therefore, the present study aimed to conduct a comparative analysis between Elevated Plus Maze (EPM) and Open Field (OF) tests as methods for evaluating mice's anxiety-like behavior, considering environmental and age variables. For this, eighty Female albino Swiss mice aged 6, 12, and 18 months were housed in an impoverished environment (IE) and enriched environment (EE). Following this, the animals were tested in EPM and OF tests. The environment and age affect the anxiety-like behavior of the mice in the OF, with a difference between the animals of 6 and 18 months, only in the EE (p < 0.021). However, in the EPM, it does not occur. Despite that, the environment affected the distance traveled by the mice in the EPM, where the IE animals showed greater exploratory activity than the EE, only in the 18-month group (p < 0.001). No environmental influences were detected in the OF. Concerning age, in the EPM, animals in the 18-month-old group traveled shorter distances compared to the 6-month group (p < 0.001) and the 12-month group (p < 0.001), only in EE. In turn, in the OF there was a decrease in the distance traveled in the 18-month group compared to the 6-month group (p = 0.012), only in the IE. Thus, the divergences between the results of EPM and OF instigate a better evaluation of the parameters analyzed in each test.

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Environmental Enrichment (EE) is based on the promotion of socio-environmental stimuli, which mimic favorable environmental conditions for the practice of physical activity and health. The objective of the present systematic review was to evaluate the influence of EE on pro-and anti-inflammatory immune parameters, but also in cell activation related to the innate and acquired immune responses in the brain and peripheral tissues in rodents. Three databases [PubMed (2209 articles), Scopus (1154 articles), and Science Direct (1040 articles)] were researched. After applying the eligibility criteria, articles were selected for peer review, independently, as they were identified by September 2021. The protocol for this systematic review was registered in the PROSPERO. Of the 4417 articles found, 16 were selected for this systematic review. In the brain, EE promoted a reduction in proinflammatory cytokines and chemokines. In the blood, EE promoted a higher percentage of leukocytes, an increase in CD19+ B lymphocytes, and the proliferation of Natura Killer (NK cells). In the bone marrow, there was an increase in the number of CD27- and CD11b+ mature NK cells and a reduction in CD27- and CD11b+ immature Natural Killer cells. In conclusion, EE can be an immune modulation approach and plays a key role in the prevention of numerous chronic diseases, including cancer, that have a pro-inflammatory response and immunosuppressive condition as part of their pathophysiology.

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Obesity can lead to chronic inflammation in different tissues, generating insulin and leptin resistance and alterations in glucose and lipid metabolism, favoring the development of degenerative diseases, including type II diabetes. Congruently, the inflammatory signaling inhibition prevents the development of obesity and restores insulin sensitivity. Via the enhancement of central nervous system activity, an enriched environment (EE) has beneficial effects on learning and memory as well as on immune cell functions and inflammation in different disease models. Here, we explored whether an EE can restore energy balance in obese mice that previously presented metabolic alterations. We discovered that an EE improved glucose metabolism, increased insulin signaling in liver, and reduced hepatic steatosis and inflammation, and increased lipolysis and browning in the white adipose tissue of high-fat diet (HFD)-fed mice. Finally, we found reduced inflammatory signaling and increased anorexigenic signaling in the hypothalamus of HFD-fed mice exposed to an EE. These data indicate that an EE is able to restore the metabolic imbalance caused by HFD feeding. Thus, we propose EE as a novel therapeutic approach for treating obesity-related metabolic alterations. This article has an associated First Person interview with the first author of the paper.

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Glaucoma is one of the world's most frequent visual impairment causes and leads to selective damage to retinal ganglion cells and their axons. Despite glaucoma's most accepted risk factor is increased intraocular pressure (IOP), the mechanisms behind the disease have not been fully elucidated. To date, IOP lowering remains the gold standard; however, glaucoma patients may still lose vision regardless of effective IOP management. Therefore, the exclusive IOP control apparently is not enough to stop the disease progression, and developing new resources to protect the retina and optic nerve against glaucoma is a goal of vast clinical importance. Besides pharmacological treatments, environmental conditions have been shown to prevent neurodegeneration in the central nervous system. In this review, we discuss current concepts on key pathogenic mechanisms involved in glaucoma, the effect of enriched environment on these mechanisms in different experimental models, as well as recent evidence supporting the preventive and therapeutic effect of enriched environment exposure against experimental glaucomatous damage. Finally, we postulate that stimulating vision may become a non-invasive and rehabilitative therapy that could be eventually translated to the human disease, preventing glaucoma-induced terrible sequelae resulting in permanent visual disability.

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Central nervous system (CNS) development is a very complex process that can be altered by environmental stimuli such as noise, which can generate long-term auditory and/or extra-auditory impairments. We have previously reported that early noise exposure can induce hippocampus-related behavioral alterations in postnatal day (PND) 28 adolescent rats. Furthermore, we recently found biochemical modifications in the hippocampus (HC) of these animals that seemed to endure even in more mature animals (i.e. PND35) and that have not been studied along with behavioral correlates. Thus, the aim of this work was to reveal novel data about the effects of early noise exposure on hippocampal-dependent behaviors in more mature animals. Additionally, extended enriched environment (EE) housing was evaluated to determine its capacity to induce behavioral modifications, either by its neuroprotective ability or the greater stimulation that it generates. Male Wistar rats were exposed to different noise schemes at PND7 or PND15. Upon weaning, some animals were transferred to EE whereas others were kept in standard cages. At PND35, different hippocampal-dependent behavioral assessments were performed. Results showed noise-induced behavioral changes that differed according to the scheme and age of exposure used. In addition, housing in an EE was effective either in preventing some of these changes or in inducing the appearance of new behavioral modifications. These findings suggest that CNS development would be sensitive to the effects of different type of environmental stimuli such as noise or enriched housing, leading to maladaptive behavioral changes that last even until adolescence.

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Environmental factors interfere in the neural plasticity processes. Among these, malnutrition in the early stages of life stands out as one of the main non-genetic factors that can interfere in the morphofunctional development of the nervous system. Furthermore, sensory stimulation from enriched environments (EE) also interferes with neural development. These two factors can modify areas related to memory and learning as the hippocampus, through mechanisms related to the gene expression of brain-derived neurotrophic factor (BDNF). The BDNF may interfere in synaptic plasticity processes, such as memory. In addition, these changes in early life may affect the functioning of the hippocampus during adulthood through mechanisms mediated by BDNF. Therefore, this study aims to conduct a literature review on the effects of early malnutrition on memory and the relationship between the underlying mechanisms of EE, BDNF gene expression, and memory. In addition, there are studies that demonstrate the effect of EE reversal on exposure to changes in the functioning of hippocampal malnutrition in adult rats that were prematurely malnourished. Thereby, evidence from the scientific literature suggests that the mechanisms of synaptic plasticity in the hippocampus of adult animals are influenced by malnutrition and EE, and these alterations may involve the participation of BDNF as a key regulator in memory processes in the adult animal hippocampus.

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