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Overweight induced by high-fat diet (HFD) represents one of the major health concerns in modern societies, which can cause lasting peripheral and central metabolic disorders in all age groups. Specifically, childhood obesity could lead to life-long impact on brain development and functioning. On the other hand, environmental enrichment (EE) has been demonstrated to be beneficial for learning and memory. Here, we explored the impact of high-fat diet on olfaction and organization of olfactory bulb cells in adolescent mice, and the effect of EE intervention thereon. Puberty mice (3-week-old) fed with HFD for 10 weeks exhibited poorer odor sensitivity and olfactory memory relative to controls consuming standard chows. The behavioral deficits were rescued in the HFD group with EE intervention. Neuroanatomically, parvalbumin (PV) interneurons in the olfactory bulb (OB) were reduced in the HFD-fed animals relative to control, while EE intervention also normalized this alteration. In contrast, cells expressing calbindin (CB), doublecortin (DCX) in the OB were not altered. Our findings suggest that PV interneurons may play a crucial role in mediating the HFD-induced olfactory deficit in adolescent mice, and can also serve a protective effect of EE against the functional deficit.

Including Indirect Genetic Effects (IGE) in breeding programs to reduce aggression in group housed animals has been proposed. However, the effect of selection for IGE for growth on animal metabolism and physiology is unknown. The purpose of this study was twofold: (1) To investigate the effects of this new breeding method along with two housing (barren and straw), coping style (high and low resisters) and sex (female and castrated males) options on the metabolome profile of pigs. (2) To identify and map biological processes associated with a regrouping test at 9 weeks of age. We used Nuclear Magnetic Resonance to quantify 49 serum metabolites at week 8, 9 and 22. Also, we quantified 3 catecholamines (tyramine, epinephrine, phenylethylamine) and serotonin and three water soluble vitamins (B2, B5 and B7). Overall, no significant differences were observed between negative and positive IGE animals. The magnitude of change (delta) of many metabolites as a response to the regrouping test was significantly affected by IGE, especially that of the amino acids (P

The multifactorial etiology of stress-related disorders necessitates a constant interrogation of the molecular convergences in preclinical models of stress that use disparate paradigms as stressors spanning from environmental challenges to genetic predisposition to hormonal signaling. Using RNA-sequencing, we investigated the genomic signatures in the ventral hippocampus common to mouse models of stress. Chronic oral corticosterone (CORT) induced increased anxiety- and depression-like behavior in wild-type male mice and male mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met, a variant associated with genetic susceptibility to stress. In a separate set of male mice, chronic social defeat stress (CSDS) led to a susceptible or a resilient population, whose proportion was dependent on housing conditions, namely standard housing or enriched environment. Rank-rank-hypergeometric overlap (RRHO), a threshold-free approach that ranks genes by their p value and effect size direction, was used to identify genes from a continuous gradient of significancy that were concordant across groups. In mice treated with CORT and in standard-housed susceptible mice, differentially expressed genes (DEGs) were concordant for gene networks involved in neurotransmission, cytoskeleton function, and vascularization. Weighted gene co-expression analysis generated 54 gene hub modules and revealed two modules in which both CORT and CSDS-induced enrichment in DEGs, whose function was concordant with the RRHO predictions, and correlated with behavioral resilience or susceptibility. These data showed transcriptional concordance across models in which the stress coping depends upon hormonal, environmental, or genetic factors revealing common genomic drivers that embody the multifaceted nature of stress-related disorders.

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.

Background The underlying neurobiology of early-life stress (ELS)-induced major depressive disorder is not clearly understood. Methods In this study, we used maternal separation (MS) as a rodent model of ELS and tested whether microRNAs (miRNAs) target serotonin genes to regulate ELS-induced depression-like behavior and whether this effect is sex dependent. We also examined whether environmental enrichment prevents susceptibility to depression- and anxiety-like behavior following MS and whether enrichment effects are mediated through serotonin genes and their corresponding miRNAs. Results MS decreased sucrose preference, which was reversed by enrichment. Males also exhibited greater changes in forced swim climbing and escape latency tests only following enrichment. Slc6a4 and Htr1a were upregulated in the frontal cortex following MS. In male MS rats, enrichment slightly reversed Htr1a expression to levels similar to control rats. miR-200a-3p and miR-322-5p, which target SLC6A4, were decreased by MS, but not significantly. An HTR1A-targeting miRNA, miR-320-5p, was also downregulated by MS and showed slight reversal by enrichment in male animals. miR-320-5p targeting of Htr1a was validated in vitro using SHSY neuroblastoma cell lines. Conclusions Altogether, this study implicates miRNA interaction with the serotonin pathway in ELS-induced susceptibility to depression-related reward deficits. Furthermore, because of its recovery by enrichment in males, miR-320 may represent a viable sex-specific target for reward-related deficits in major depressive disorder.

Chronic stress causes dendritic atrophy of neurons within the hippocampus and medial prefrontal cortex. In this report, we show that chronic stress leads to reduced long-term potentiation in the pathway from the hippocampus to the medial prefrontal cortex of rats; and that such reduction is rescued by enriched housing environment. Connectivity between the hippocampus and medial prefrontal cortex is proposed to be an essential substrate that is often compromised in several psychiatric disorders. Our observations suggest that a short period of complexity in the housing environment has the potential to protect the functional integrity of this important connection. Ministry of Education (MOE) This study is supported by the Ministry of Education, Singapore (# RG 46/12) to RM.

Animal welfare is critical to buffer stress in captive animals and to ensure the reliability of data from studies. The most usual environmental enrichment technique (EE) for social non-human primates is the social enrichment. However, some experimental protocols require keeping individuals isolated, thus demanding other types of EE. We tested in six adult

Objective: The purpose of this study was to investigate growth performance, carcass traits, meat quality and hair follicle development of growing Rex rabbits as affected by different environmental enrichment materials.Methods: A total of one hundred and twenty Rex rabbits were randomly assigned to four groups; reared in conventional cages (not enriched) and in enriched cages with either willow stick (WS), rubber duck, or a can containing beans (CB), for 44 days.Results: The average daily gain of the CB group was the highest and had a significant difference from that of the other groups (p

Rationale Risk factors for drug addiction include genetics, environment, and behavioral traits such as impulsivity and novelty preference (NP), which have been related to deficits in striatal dopamine (DA) D2/3-receptors (D2/3R) and heightened amphetamine (AMPH)-induced DA release. However, the influence of the early rearing environment on these behavioral and neurochemical variables is not clear. Objectives We investigated the influence of early rearing environment on striatal D2/3R availabilities and AMPH-induced DA release in relation to impulsivity, NP, and propensity to drug self-administration (SA) in “addiction-prone” Roman high- (RHA) and “addiction-resistant” Roman low-avoidance (RLA) rats. Methods Animals were reared post-weaning in either environmental enrichment (EE) or impoverishment (EI) and were assessed at adulthood for impulsivity, NP, and propensity to cocaine SA. EE and EI rats were also scanned using single-photon emission computed tomography to concurrently measure in vivo striatal D2/3R availability and AMPH-induced DA release. Results EE vs. EI was associated with heightened impulsivity and a lack of NP in both rat lines. Higher dorsal striatal D2/3R densities were found in RHA EE and higher AMPH-induced DA release in RLA EE. Both impulsivity and NP were negatively correlated to dorsal striatal D2/3R availabilities and positively correlated with AMPH-induced DA release in EI but not in EE. EE vs. EI was related to a faster rate of cocaine intake and elevated active timeout responses in RHAs. Conclusion Our results suggest non-monotonic, environment-dependent, relationships between impulsivity, NP, and D2/3R-mediated signaling, and suggest that EI vs. EE may decrease the reinforcing effects of psychostimulants in predisposed individuals.

The development of anxiety and depression due to chronic exposure to noise stress has remained as an unsolved health problem so far. Despite the studies suggesting the neuroenhancement effects of transcranial photobiomodulation (tPBM) and housing in an enriched environment (EE), the combined effects of these treatments have not been elucidated yet. Also, there is no available data on the relationship between the application of tPBM and hippocampal brain-derived neurotrophic factor (BDNF) expression in animal models of stress. The present study aims to investigate the application of the tPBM and EE (alone or in combination) on depressive- and anxiety-like behaviors in a mice model of noise stress. Mice were divided into five groups: control, noise, noise + EE, noise + tPBM, and noise + EE + tPBM. Except for the control group, other groups were subjected to 110 dB SPL white noise for 4 h/day for 14 consecutive days and received their respective treatments. Forced Swimming Test (FST) was used to evaluate depressive-like behaviors. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. BDNF, tyrosine receptor kinase B (TrkB), and cAMP response element-binding (CREB) protein levels in the hippocampus were determined by the Western blot method, and also serum corticosterone levels were assessed using an ELISA kit. Exposure to noise stress significantly elevated serum corticosterone level; downregulated hippocampal BDNF, TrkB, and CREB protein expressions; and resulted in depressive- and anxiety-like behaviors. While, the application of tPBM (810 nm wavelength, 8 J/cm2 fluence, 10 Hz pulsed wave mode), housing in EE, and their combination lowered corticosterone levels, upregulated the BDNF/TrkB/CREB signaling pathway in the hippocampus, and improved behavioral outcomes in noise stress subjected mice. Our finding revealed the improving effects of tPBM and EE on depressive and anxiety-like behaviors induced by noise stress, possibly by augmenting the BDNF/TrkB/CREB signaling pathway.

Zoo-housed animals are regularly exposed to new forms of environmental enrichment to make their lives less predictable. However, providing new enrichment can have unpredictable effects. We evaluated the effectiveness of two enrichment regimes: (1) providing only new enrichments - "Novelty" and (2) only familiar enrichments - "Familiar." In this case study, enrichment efficacy was assessed using activity budget analysis and novel object tests. The subjects were two focal animals: the golden jackal (Canis aureus) and the European badger (Meles meles). Our results suggest that both assessment methods provided similar conclusions about the animal's welfare. The "Familiar" treatment significantly increased activity and decreased abnormal behavior in the jackal's activity budget, who avoided novel objects in her baseline novel object test. The Novelty treatment resulted in the growth of time the jackal spent in the moat instead of the main enclosure, and an increase in avoidance and abnormal behaviors. In contrast, the badger demonstrated a high intensity of exploratory behavior in the baseline novel object test, and both regimes led to an increase in the activity budget of the badger. We propose that a stable, but complex enrichment can be an effective robust tool to increase animal welfare, but its efficacy depends on the novelty preference of individual animals. A novel object test can be a rapid tool to assess individual animals' novelty preferences, and this information may help to choose optimal enrichment regimes for individual animals.

One critial point in the Laboratory Animal Science (CAL) is the non-invasive evaluation of Animal Welfare (BEA). The detection (predictive or diagnostic) of the presence of suffering in mice when used for scientific purposes is a gap. The manuscrip aim to create a technical-scientific form to preditive presence of suffering in mice lab, based on the principle of Refinement of the 3Rs and BEA monitoring. Our methodology was based in usual environmental enrichment the objects, the trapeze. From these observations, our study hypothesis emerged, which was, the creation of the #1 Trap prototype and the measurement through the daily counting of the number of trapeze use during 15 minutes. Experimental acute infection by Trypanosoma cruzi was experimental model in Swiss Webster mice. Our results described that, after division into four groups: [N] without infection and [Inf] mice infected and without treatment. The predictive statistical difference was observed on the 11th day post infection (dpi) when compared ([N]: 72±18.5 Events number/15min) and ([Inf]: 32±13.1 Events number/15min) (p ≤ 0.05). The 21st dpi was the most severe time point ([N]: 75±17.3 and [Inf]: 11±5.1 Events number/15min, respectively) (p ≤ 0.05). So, our results suggest the #1 Trap prototype has predictive and monitoring capacity for experimental disease course. It makes it possible to prevent suffering and preservation of mice welfare during acute T. cruzi experimental model.

The aim of the present study was to evaluate the behaviour of Meriz goats using environmental enrichment technique. Sixteen goats aged two-four years, were divided into two equal groups, one group was placed in a stall without any enrichment (control), while the other group placed in another stall with enrichment. The enriched stall had six objects including canopy, grooming brush, suspended tire, trunk of tree, and plastic PET bottle suspended and freely move on the floor. The goats’ behaviours were observed for eighty minutes in the morning and eighty minutes in the evening for fifteen consecutive days. Focal-animal sampling methods were used to record the behaviours, in which each animal was observed for ten-minutes period each day. Results revealed that the animals of enriched environment group displayed lower frequency of stereotypic and abnormal behaviour than control group. The mean frequencies of the groups were significantly different (P

—This review summarizes the data on plastic restructuring in animals under the influence of the enriched environment (EE). The EE includes three main components: sensory stimulation, social stimulation, and physical activity. Each of these components has its own peculiarities and specifics of influence but all of them have positive effects on the organism. The first part of this review summarizes the molecular-cellular mechanisms of EE influence on neurogenesis, neurotrophic factors, and synaptogenesis. The second part presents data on the effects of EE on plastic restructuring of synaptic transmission in hippocampal neurons, induction and maintenance of long-term potentiation and long-term depression of responses of neurons in the dentate gyrus and CA1 area of hippocampus, the neurochemical mechanisms of the EE influence, and the results of the use of transgenic animals. In the third and fourth parts, we consider the influence of EE on learning and memory in normal animals and in animals with disturbances of cognitive, emotional, and motor functions.

Environmental enrichment (EE) has been successfully implemented in human rehabilitation settings. However, the mechanisms underlying its success are not understood. Incorporating components of EE protocols into our animal models allows for the exploration of these mechanisms and their role in mitigation. Using a mouse model of maternal immune activation (MIA), the present study explored disruptions in social behavior and associated hypothalamic pituitary adrenal (HPA) axis functioning, and whether a supportive environment could prevent these effects. We show that prenatal immune activation of toll-like receptor 3, by the viral mimetic polyinosinic-polycytidylic acid (poly(I:C)), led to disrupted maternal care in that dams built poorer quality nests, an effect corrected by EE housing. Standard housed male and female MIA mice engaged in higher rates of repetitive rearing and had lower levels of social interaction, alongside sex-specific expression of several ventral hippocampal neural stress markers. Moreover, MIA males had delayed recovery of plasma corticosterone in response to a novel social encounter. Enrichment housing, likely mediated by improved maternal care, protected against these MIA-induced effects. We also evaluated c-Fos immunoreactivity associated with the novel social experience and found MIA to decrease neural activation in the dentate gyrus. Activation in the hypothalamus was blunted in EE housed animals, suggesting that the putative circuits modulating social behaviors may be different between standard and complex housing environments. These data demonstrate that augmentation of the environment supports parental care and offspring safety/security, which can offset effects of early health adversity by buffering HPA axis dysregulation. Our findings provide further evidence for the viability of EE interventions in maternal and pediatric settings.Highlights‐Environmental enrichment (EE) protocols are used clinically to promote rehabilitation‐Use of EE in animal models may identify mechanisms underlying clinical successes‐Maternal immune activation (MIA) decreased social engagement; this effect was blocked by EE‐MIA reduced c-Fos activation in the dentate gyrus, while EE reduced activation in the hypothalamus, in response to social stimuli‐EE inhibited MIA-induced HPA dysregulation in ventral hippocampus

Environmental enrichment (EE) has been a widely used tool to improve animal welfare, as well as to study brain plasticity. Traditional EE settings in the field of neuroscience employ highly complex cages with numerous objects and increased space, whereas more simple additions included for the control treatment are rarely considered in the experimental design. This leads to a lack of consistency of what neuroscientists designate as "standard housing," which might compromise the reproducibility of the results. Therefore, we employed standard-sized cages to study how different EE configurations can affect several biological markers of animal welfare. We first compared barren cages with cages containing nest material and a cardboard roll or cages having a complex set of elements. For this purpose, we studied anxiety-like behavior, corticosterone metabolites in feces, and cell survival in the hippocampus. Complex enrichment (CE) increased the concentration of corticosterone metabolites while also decreasing anxiety-like behavior. Interestingly, both simple and CEs were able to promote cell survival in the hippocampus, and this measure was positively correlated to corticosterone metabolites. Furthermore, in a second experiment, one of the elements of the CE was able to reduce anxiety-like behavior and blood glucose reactivity after exposure to a stressful situation. Altogether, this study calls attention about how sensitive experimental outcomes are to these simple EE elements. Even though EE is recommended by most guidelines for the care and use of laboratory animals, a detailed analysis of the EE protocol that is going to be implemented is highly encouraged. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions., Decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Here the authors provide evidence that environmental enrichment delays age-related DNA methylation alterations in the mouse hippocampus.

Social stressors produce neurobiological and emotional consequences in social species. Environmental interventions, such as environmental enrichment and exercise, may modulate physiological and behavioral stress responses. The present study investigated the benefits of environmental enrichment and exercise against social stress in the socially monogamous prairie vole. Female prairie voles remained paired with a sibling (control) or were isolated from a sibling for 4 weeks. The isolated groups were separated into isolated sedentary, isolated with environmental enrichment, and isolated with both enrichment and exercise conditions. Behaviors related to depression, anxiety, and sociality were investigated using the forced swim test (FST), elevated plus maze (EPM), and a social crowding stressor (SCS), respectively. cFos expression was evaluated in stress-related circuitry following the SCS. Both enrichment and enrichment with exercise protected against depression-relevant behaviors in the FST and social behavioral disruptions in the SCS, but only enrichment with exercise protected against anxiety-related behaviors in the EPM and altered cFos expression in the hypothalamic paraventricular nucleus in isolated prairie voles. Enrichment may alleviate emotion-related and social behaviors, however physical exercise may be an important component of environmental strategies for protecting against anxiety-related behaviors and reducing neural activation as a function of social stress.

Xenopus laevis frogs have long been widely used as an animal model in research. However, their husbandry has scarcely evolved, although they are prone to environmental stress. Environmental enrichment has been shown to improve animal welfare and adaptation, as well as zootechnical indices, which have become very important in recent years. The aim of this study was to examine the preferences of X. laevis frogs for various elements of environmental enrichment: opaque polyvinyl chloride (PVC) pipes, artificial plants and clear spaces. A preferential study was conducted in two different tanks, each divided into six parts, where the two enrichment elements were rotated. Ten X. laevis frogs were introduced into each tank, and the number of frogs was counted in each division three times per day for six weeks. The number of frogs in the different spaces and different enrichments was evaluated through a Poisson regression model. Frogs preferred plants to PVC pipes and clear spaces regardless of the position of the enrichment element, time and day. This indicates that artificial plants should be used as the enrichment element rather than the commonly used PVC pipes. In addition, the use of plants facilitates the observation of frogs without disturbing them and reduces the accumulation of detritus, as it occurs inside the pipes.

Environmental enrichment supports the well-being and welfare of captive animals. In the current study, the most suitable form of enrichment device for captive green turtles (Chelonia mydas) was investigated, to support head-start programs rearing turtles for release into their natural habitat. Fifteen-day-old turtles (113-114 g initial weight, n = 75) were randomly distributed into 15 experimental plastic tanks, comprising 5 treatments across three pools of each condition. The turtles in the experimental groups were exposed to four forms of enrichment devices (RS, ring shape; HSQS, hollow square shape; SS, sphere shape; CS, cylinder shape), and their outcomes related to growth, feed utilization, behavior, reduction of injury from conspecifics, and several health parameters were compared to those of a control group. At the end of the 10-week trial, the growth and feed utilization parameters did not differ across the five groups (p > .05). Of the turtles in the experimental treatments, those in the RS treatment spent more time interacting with the enrichment device, followed by the HSQS group. The percentage of wounds suffered through biting was significantly reduced in the groups exposed to enrichment devices, notably in the turtles exposed to the SS device, followed by the RS device. Significant differences between experimental groups in the specific activities of the major intestinal protein-digesting enzymes (trypsin and chymotrypsin) were observed. There were no effects noted in the hematological parameters and the main carapace elemental profile as compared to the control treatment. These findings suggest that the RS device is most appropriate in enriching the environment of juvenile green turtles in captivity programs, as well as in zoos or aquaria.

Recent studies have shown beneficial effects of environmental enrichment (EE) for zebrafish, while infection of zebrafish with the common pathogen Pseudoloma neurophilia has negative effects. This study investigates the effects of P. neurophilia infection and EE in housing and breeding tanks on measures of behavior, growth, and reproduction. Zebrafish were socially housed and were either infected, P. neurophilia-infected (PNI) (n = 12 tanks), or SPF for P. neurophilia (SPF) (n = 24 tanks). Fish were housed with or without EE, which consisted of placing plastic plants in the tanks; sprigs from plants were placed in half of the breeding tanks for half of breedings, alternating breeding tanks without EE weekly. Behavioral testing included the Novel Tank Diving Test (NTT) and Light/Dark Preference Test (LDT) conducted prior to breeding. At the end of the study, biometric data were collected. Histopathology and molecular analysis for common diseases in fish confirmed that SPF fish remained SPF and that fish from all PNI tanks were infected. PNI fish produced significantly fewer eggs and had lower body weights and lengths than did SPF fish. Fish with EE had longer body lengths, than did fish without EE, and male fish had longer body lengths than female fish. The biometric results and reproductive measures show that SPF fish exhibited better growth and suggest that EE in housing tanks could improve fish growth. The behavioral test results were inconclusive regard- ing whether infection status or EE altered anxiety-like behavior. Our results support other recent studies showing negative effects of P. neurophilia infection on zebrafish.

Maternal opioids abuse has some deleterious consequences on next generations. Besides, children's rearing conditions can affect the behavioral states and brain plasticity in their later life. In the present study, we investigated the effects of maternal morphine (MOR) treatment and post-weaning rearing conditions on memory, pain threshold, and the ventral striatum dopaminergic activity in male offspring. Female Wistar rats were treated twice daily either with escalating doses of MOR or with normal saline (NS) one week before mating, during pregnancy and lactation. After weaning, the male pups were assigned to six groups and then raised for an 8-week period under three different conditions: standard (STD), isolated (ISO) or enriched environment (EE). The behavioral tests, including passive avoidance task, novel object recognition, and tail-flick test, were also performed. Moreover, the ventral striatum dopamine's content (DA), mRNA expressions of dopamine receptor 1(D1R) and dopamine receptor 2 (D2R), and dopamine transporter (DAT) were evaluated. The obtained data showed that maternal MOR exposure and post-weaning social isolation could dramatically impair memory in offspring, while EE could reverse these adverse outcomes. Moreover, results of tail flick latency indicated the increased pain threshold in EE animals. At molecular level, maternal MOR injections and social isolation reduced DA levels and altered expressions of D1R, D2R, and DAT within the ventral striatum of these male offspring. However, post-weaning EE partially buffered these changes. Our finding signified the effects of maternal MOR exposure and social isolation on the behaviors and neurochemistry of brain in next generation, and it also provided evidence on reversibility of these alterations following EE.

The feed additive ractopamine, a β-adrenergic agonist, has been approved for use in livestock for nearly 2 decades. Studies of its possible adverse effects in humans have concentrated exclusively on cardiovascular disease and cardiovascular functional disorders in the past. In this article, whether and how ractopamine may affect neurodegeneration, either to promote or to reduce the incidence of Alz­heimer disease, will be discussed based on the recent controversial findings that β-adrenoreceptor activation not only can stimulate Alzheimer-pathogenic amyloid-β accumulation but also are able to enhance hippocampal neurogenesis and ameliorate mouse memory deficits in independent laboratory studies. Furthermore, environmental enrichment has been found to prevent impairment of memory-related hippocampal long-term potentiation and microglia-mediated neuroinflammation induced by amyloid-β. These beneficial effects are achieved mainly through enhanced β-adrenergic signaling and can be imitated by β agonist isoprotenerol. Finally, it has been demonstrated that the β-adrenergic agonist salbutamol could bind directly to tau protein and interfere with the tau filament formation seen in the prodromal phase of Alzheimer disease. These complex but interesting issues lead to contradictory speculations of possible effects of ractopamine residue in meat on Alzheimer disease. Hypotheses derived from this review surely deserve carefully designed laboratory investigations and clinical studies in the future.

Background Teleost fish are known to respond to environmental manipulation, which makes them an ideal model animal for testing relationships between the environment and behavior. The Siamese fighting fish, Betta splendens, is a solitary, highly territorial fish that displays fierce stereotyped aggressive behavior toward conspecifics or members of other species. Adult fish, especially males, are generally housed in isolation in captivity. Here we report evidence that an enriched rearing environment can decrease the level of aggression in bettas and enable adults to be housed in groups. Results B. splendens individuals were hatched in our laboratory and raised in groups in an enriched environment. At the juvenile or subadult stage, some individuals were relocated to a poor environment and kept in isolation. To evaluate aggression, a mirror-image test was conducted at the juvenile, subadult, and adult stages for each fish, and body parameters as well as plasma concentrations of 11-ketotestosterone, estradiol, and cortisol were evaluated. Male and female adult bettas raised in a group showed lower levels of aggression than other adult fish. The magnitude of threatening behavior was greater in adult bettas isolated as subadults, whereas the magnitude of fighting behavior was grater in adult bettas isolated as juveniles. The influence of rearing conditions on behavior was greater in females than in males. Plasma cortisol concentrations of adult bettas isolated as subadults after the mirror-image test were higher than those in other experimental groups. Adult males isolated as subadults had significantly higher plasma concentrations of 11-ketotestosterone than males raised in a group and isolated as juveniles. Females isolated as subadults had a higher gonadosomatic index than females raised in a group and females isolated as juveniles. Conclusions These results indicate that bettas can be kept in a group under enriched environments and that the timing of isolation influences the aggression and sexual maturity of bettas. Female and male bettas responded differently to environmental manipulation. Judging from their level of sexual maturity, bettas isolated as subadults show proper development.

Throughout life, sensory systems adapt to the sensory environment to provide optimal responses to relevant tasks. In the case of a developing system, sensory inputs induce changes that are permanent and detectable up to adulthood. Previously, we have shown that rearing rat pups in a complex acoustic environment (spectrally and temporally modulated sound) from postnatal day 14 (P14) to P28 permanently improves the response characteristics of neurons in the inferior colliculus and auditory cortex, influencing tonotopical arrangement, response thresholds and strength, and frequency selectivity, along with stochasticity and the reproducibility of neuronal spiking patterns. In this study, we used a set of behavioral tests based on a recording of the acoustic startle response (ASR) and its prepulse inhibition (PPI), with the aim to extend the evidence of the persistent beneficial effects of the developmental acoustical enrichment. The enriched animals were generally not more sensitive to startling sounds, and also, their PPI of ASR, induced by noise or pure tone pulses, was comparable to the controls. They did, however, exhibit a more pronounced PPI when the prepulse stimulus was represented either by a change in the frequency of a background tone or by a silent gap in background noise. The differences in the PPI of ASR between the enriched and control animals were significant at lower (55 dB SPL), but not at higher (65-75 dB SPL), intensities of background sound. Thus, rearing pups in the acoustically enriched environment led to an improvement of the frequency resolution and gap detection ability under more difficult testing conditions, i.e., with a worsened stimulus clarity. We confirmed, using behavioral tests, that an acoustically enriched environment during the critical period of development influences the frequency and temporal processing in the auditory system, and these changes persist until adulthood.

Huntington's disease (HD) is a neurodegenerative disorder caused by a trinucleotide repeat expansion in the huntingtin gene. Transcriptomic dysregulations are well-documented in HD and alterations in small non-coding RNAs (sncRNAs), particularly microRNAs (miRNAs), could underpin that phenomenon. Additionally, environmental enrichment (EE), which is used to model a stimulating lifestyle in pre-clinical research, has been shown to ameliorate HD-related symptoms. However, the mechanisms mediating the therapeutic effects of EE remain largely unknown. This study assessed the effect of EE on sncRNA expression in the striatum of female R6/1 transgenic HD mice at 12 weeks (prior to over motor deficits) and 20 weeks (fully symptomatic) of age. When comparing wild-type and R6/1 mice in the standard housing condition, we found 6 and 64 miRNAs that were differentially expressed at 12 and 20 weeks of age, respectively. The 6 miRNAs (miR-132, miR-212, miR-222, miR-1a, miR-467a, and miR-669c) were commonly dysregulated at both time points. Additionally, genotype had minor effects on the levels of other sncRNAs, in particular, 1 piRNA was dysregulated at 12 weeks of age, and at 20 weeks of age 11 piRNAs, 1 tRNA- and 2 snoRNA-derived fragments were altered in HD mice. No difference in the abundance of other sncRNA subtypes, including rRNA- and snRNA- derived fragments, were observed. While EE improved locomotor symptoms in HD, we found no effect of the housing condition on any of the sncRNA populations examined. Our findings show that HD mainly affects miRNAs and has a minor effect on other sncRNA populations. Furthermore, the therapeutic effects of EE are not associated with the rescue of these dysregulated sncRNAs and may therefore exert these experience-dependent effects via other molecular mechanisms.

Different neuronal alterations within glutamatergic system seem to be crucial for developing of cocaine-seeking behavior. Cocaine exposure provokes a modulation of the NMDA receptor subunit expression in rodents, which probably contributes to cocaine-induced behavioral alterations. The aim of this study was to examine the composition of the NMDA receptor subunits in the brain structures in rats with the history of cocaine self-administration after cocaine abstinence (i) in an enriched environment, (ii) in an isolated condition, (iii) with extinction training, or (iv) without instrumental task, as well as the Grin1 (encoding GluN1) and Grin2A (encoding GluN2A) gene expression were evaluated after 10-day extinction training in rat brain structures. In the present study, we observed changes only following cocaine abstinence with extinction training, when the increased GluN2A subunit levels were seen in the postsynaptic density fraction but not in the whole homogenate of the prelimbic cortex (PLC) and dorsal hippocampus (dHIP) in rats previously self-administered cocaine. At the same time, extinction training did not change the Grin1 and Grin2A gene expression in these structures. In conclusion, NMDA receptor subunit modulation observed following cocaine abstinence with extinction training may represent a potential target in cocaine-seeking behavior.

The addition of new neurons to existing neural circuits in the adult brain remains of great interest to neurobiology because of its therapeutic implications. The premier model for studying this process has been the hippocampal dentate gyrus in mice, where new neurons are added to mature circuits during adulthood. Notably, external factors such as an enriched environment (EE) and exercise markedly increase hippocampal neurogenesis. Here, we demonstrate that EE acts by increasing fibroblast growth factor receptor (FGFR) function autonomously within neurogenic cells to expand their numbers in adult male and female mice. FGFRs activated by EE signal through their mediators, FGFR substrate (FRS), to induce stem cell proliferation, and through FRS and phospholipase Cγ to increase the number of adult-born neurons, providing a mechanism for how EE promotes adult neurogenesis.SIGNIFICANCE STATEMENTHow the environment we live in affects cognition remains poorly understood. In the current study, we explore the mechanism underlying the effects of an enriched environment on the production of new neurons in the adult hippocampal dentate gyrus, a brain area integral in forming new memories. A mechanism is provided for how neural precursor cells in the adult mammalian dentate gyrus respond to an enriched environment to increase their neurogenic output. Namely, an enriched environment acts on stem and progenitor cells by activating fibroblast growth factor receptor signaling through phospholipase Cγ and FGF receptor substrate proteins to expand the pool of precursor cells.

Macroenvironmental factors, including a patient’s physical and social environment, play a role in cancer risk and progression. Our previous preclinical studies have shown that the enriched environment (EE) confers anti-obesity and anti-cancer phenotypes that are associated with enhanced adaptive immunity and are mediated by brain-derived neurotrophic factor (BDNF). Natural killer (NK) cells have anti-cancer and anti-viral properties, and their absence or depletion is associated with inferior clinical outcomes. In this study, we investigated the effects of EE on NK cell maturation following their depletion. Mice living in EE displayed a higher proportion of NK cells in the spleen, bone marrow, and blood, compared to those living in the standard environment (SE). EE enhanced NK cell maturation in the spleen and was associated with upregulation of BDNF expression in the hypothalamus. Hypothalamic BDNF overexpression reproduced the EE effects on NK cell maturation in secondary lymphoid tissues. Conversely, hypothalamic BDNF knockdown blocked the EE modulation on NK cell maturation. Our results demonstrate that a bio-behavior intervention enhanced NK cell maturation and was mediated at least in part by hypothalamic BDNF.

Environmental factors such as stress drive the development of drug addiction in genetically vulnerable individuals; the genes underlying this vulnerability are unknown. One strategy for uncovering these genes is to study the impact of environmental manipulation on high-throughput phenotypes that predict drug use and addiction-like behaviors. In the present study, we assessed the viability of this approach by evaluating the relative effects of environmental enrichment and isolation housing on three high-throughput phenotypes known to predict variation on distinct aspects of intravenous drug self-administration. Prior to behavioral testing, male and female C57BL/6J and DBA/2J mice (BXD founders) were housed in enrichment or isolation for ten weeks beginning at weaning. Enrichment significantly reduced novelty reactivity; this effect was significantly more robust in C57BL/6J mice relative to DBA/2J mice. Enrichment significantly reduced novelty preference; this effect was significantly dependent on novel environment characteristics and was significantly more robust in DBA/2J mice relative to C57BL/6J mice. Enrichment significantly increased anxiety; this effect was not strain-dependent. Collectively, these data indicate that (1) environmental enrichment influences novelty reactivity, novelty preference, and anxiety via distinct genetic mechanisms in mice, and (2) the BXD panel can be used to discover the genetic and epigenetic mechanisms underlying this phenomenon.

The environment provided for animals in captivity is less complex than its natural habitat, which generates a stressful condition. Environmental enrichment tries to meet the animals’ ethological an...

Synaptic deficit-induced excitation and inhibition (E/I) imbalance have been implicated in the pathogenesis of schizophrenia. Using in vivo two-photon microscopy, we examined the dynamic plasticity of dendritic spines of pyramidal neurons (PNs) and "en passant" axonal bouton of parvalbumin-expressing interneurons (PVINs) in the frontal association (FrA) cortex in two adolescent mouse models with schizophrenia-like behaviors. Simultaneous imaging of PN dendritic spines and PV axonal boutons showed that repeated exposure to N-methyl-D-aspartate receptor (NMDAR) antagonist MK801 during adolescence disrupted the normal developmental balance of excitatory and inhibitory synaptic structures. This MK801-induced structural E/I imbalance significantly correlated with animal recognition memory deficits and could be ameliorated by environmental enrichment (EE). In addition, selective chemogenetic activation of PVINs in the FrA mimicked the effects of EE on both synaptic plasticity and animal behavior, while selective inhibition of PVIN abolished EE's beneficial effects. Electrophysiological recordings showed that chronic MK801 treatment significantly suppressed the frequency of mEPSC/mIPSC ratio of layer (L) 2/3 PNs and significantly reduced the resting membrane potential of PVINs, the latter was rescued by selective activation of PVINs. Such manipulations of PVINs also showed similar effects in PV-Cre; ErbB4fl/fl animal model with schizophrenia-like behaviors. EE or selective activation of PVINs in the FrA restored behavioral deficits and structural E/I imbalance in adolescent PV-Cre; ErbB4fl/fl mice, while selective inhibition of PVINs abolished EE's beneficial effects. Our findings suggest that the PVIN activity in the FrA plays a crucial role in regulating excitatory and inhibitory synaptic structural dynamics and animal behaviors, which may provide a potential therapeutic target for schizophrenia treatment.

Fasudil, a Rho-associated protein kinase (ROCK) inhibitor, has a protective effect on the central nervous system. In addition, environmental enrichment is a promising technique for inducing the recovery of motor impairments in ischemic stroke models. The present study aimed to explore whether environmental enrichment combined with fasudil can facilitate motor function recovery and induce cortical axonal regeneration after stroke. First, a mouse model of ischemic cerebral stroke was established by photochemical embolization of the left sensorimotor cortex. Fasudil solution (10 mg/kg per day) was injected intraperitoneally for 21 days after the photothrombotic stroke. An environmental enrichment intervention was performed on days 7-21 after the photothrombotic stroke. The results revealed that environmental enrichment combined with fasudil improved motor function, increased growth-associated protein 43 expression in the infarcted cerebral cortex, promoted axonal regeneration on the contralateral side, and downregulated ROCK, p-LIM domain kinase (LIMK)1, and p-cofilin expression. The combined intervention was superior to monotherapy. These findings suggest that environmental enrichment combined with fasudil treatment promotes motor recovery after stroke, at least partly by stimulating axonal regeneration. The underlying mechanism might involve ROCK/LIMK1/cofilin pathway regulation. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 20160858A232) on February 24, 2016.

Environmental enrichment for mice lags behind the standard enrichment offered to other laboratory rodents due to concerns about environmental variability and, in specific contexts, aggression. Our objective in this study was to evaluate concerns that the introduction of structural enrichment in the form of a single red acrylic mouse tunnel into murine housing may confound study findings. We measured effects on anxiety-like behaviors (elevated zero maze and open field activity), hippocampal neurogenesis, body weight gain, and physiologic markers of stress (adrenal gland weight, plasma corticosterone concentration, and neutrophil:lymphocyte ratio). Male and female C57BL/6J mice were randomly assigned to one of 2 groups: a standard-housed control group with enrichment consisting of paper nesting material, or an enriched group that received a single acrylic tunnel in addition to nesting material. All results fell within biologically normal ranges regardless of treatment, and variability (standard deviation) was not significantly different between groups for any measure. Mice in the enriched group showed modest differences during open field testing suggestive of decreased anxiety, traveling farther and depositing fewer fecal boli than standard-housed mice. Male mice in the tunnel-enriched group gained more body weight than standard-housed male mice. No significant effects by treatment were found in neurogenic or physiologic parameters. These results indicate that provision of simple structural enrichment is unlikely to have confounding effects on murine anxiety-like behaviors, neurogenesis, body weight gain, or physiologic parameters. We therefore recommend the inclusion of simple structural enrichment, such as an acrylic tunnel, to the standard environmental enrichment of social housing and nesting material for mice.

Made available in DSpace on 2021-06-25T10:15:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Objective: The effect of environmental enrichment on the behaviour of piglets in the nursery phase was evaluated. Methods: A total of 450 hybrid pigs (21 day old), including both females and uncastrated males, weighing approximately 6 kg, were distributed in a completely randomised design with 3 treatments and 3 replicates of 50 animals each. The treatments were: I) pen without environmental enrichment (control), ii) treatment consisting of continuous environmental enrichment (CEE) with rubber balls throughout the experimental period, and iii) treatment consisting of environmental enrichment with washed balls (EEWB) during the whole experimental period which were removed daily for washing. For the behavioural evaluation, 10 animals were randomly selected per replicate. The behavioural assessments were performed once a week, from 8 am to 6 pm, using images captured with a video camera. The data were submitted to non-parametric analyses, the means were compared using the Bonferroni test, and Person's correlations were also calculated. Results: A statistical difference (p = 0.001) was observed in the B5 (playful) behaviour; the animals in the EEWB treatment group had a higher frequency of this behaviour than animals in the control treatment group. The animals in the control group showed a higher frequency of B7 behaviour (lying down) (p = 0.026) than those in the EEWB and CEE treatment groups. The animals in the control group had a higher frequency of the B9 (belly nosing) behaviour than those in the EEWB group (p = 0.015). There was a tendency towards a higher frequency of behaviour B3 (walking in the pen) (p = 0.067) when the animals received the control treatment than treatments EEWB or CEE. Conclusion: The use of an enriching object improved the animal welfare and altered the correlation between the evaluated behaviours compared to the animals that did not have environmental enrichment. Department of Animal Science Federal University of Technology - Paraná (UTFPR) Campus Dois Vizinhos School of Veterinary Medicine and Animal Science São Paulo State University (UNESP) School of Veterinary Medicine and Animal Science São Paulo State University (UNESP)

Adverse environments during early life may lead to different neurophysiological and behavioral consequences, including depression and learning and memory deficits that persist into adulthood. Previously, we demonstrated that exposure to an enriched environment during adolescence mitigates the cognitive impairment observed after maternal separation in a task-specific manner. However, underlying neural mechanisms are still not fully understood. The current study examines the effects of neonatal maternal separation (MS) and postweaning environmental enrichment (EE) on spatial learning and memory performance in a short version of the Barnes Maze, active and passive behaviors in the forced swim test, and on TrkB/BDNF receptor expression in the hippocampus. Our results revealed that MS impaired acquisition learning and that enriched rats performed better than non-enriched rats in acquisition trials, regardless of early conditions. During the probe, enriched-housed rats demonstrated better performance than those reared in standard conditions. No significant differences between groups were found in the forced swim test. Both MS and EE increase full-length TrkB expression, and the combination of MS and EE treatment caused the highest levels of this protein expression. Similarly, truncated TrkB expression was higher in the MS/EE group. Animal facility rearing (AFR) non-enriched groups present the lowest activation of phosphorylated Erk, a canonical downstream kinase of TrkB signaling. Taken together, our results demonstrate the importance of enriched environment as an intervention to ameliorate the effects of maternal separation on spatial learning and memory. TrkB/BDNF signaling could mediate neuroplastic changes related to learning and memory during exposure to enriched environment.

Rationale: Stroke is a leading cause of adult disability worldwide, but no drug provides functional recovery during the repair phase. Accumulating evidence demonstrates that environmental enrichment (EE) promotes stroke recovery by enhancing network excitability. However, the complexities of utilizing EE in a clinical setting limit its translation. Methods: We used multifaceted approaches combining electrophysiology, chemogenetics, optogenetics, and floxed mice in a mouse photothrombotic stroke model to reveal the key target of EE-mediated stroke recovery. Results: EE reduced tonic gamma-aminobutyric acid (GABA) inhibition and facilitated phasic GABA inhibition in the peri-infarct cortex, thereby promoting network excitability and stroke recovery. These beneficial effects depended on GAT-1, a GABA transporter regulating both tonic and phasic GABA signaling, as EE positively regulated GAT-1 expression, trafficking, and function. Furthermore, GAT-1 was necessary for EE-induced network plasticity, including structural neuroplasticity, input synaptic strengthening in the peri-infarct cortex, output synaptic strengthening in the corticospinal tract, and sprouting of uninjured corticospinal axons across the midline into the territory of denervated spinal cord, and functional recovery from stroke. Moreover, restoration of GAT-1 function in the peri-infarct cortex by its overexpression showed similar beneficial effects on stroke recovery as EE exposure. Conclusion: GAT-1 is a key molecular substrate of the effects of EE on network excitability and consequent stroke recovery and can serve as a novel therapeutic target for stroke treatment during the repair phase.

The mechanisms of long-term memory formation and ways to improve it (in the case of its impairment) remain an extremely difficult problem yet to be solved. Over the recent years, much attention has been paid to microRNAs in this regard. MicroRNAs are unique endogenous non-coding RNAs about 22 nucleotides in length; each can regulate translation of hundreds of messenger RNA targets, thereby controlling entire gene networks. MicroRNAs are widely represented in the central nervous system. A large number of studies are currently being conducted to investigate the role of microRNAs in the brain functioning. A number of microRNAs have been shown to be involved in the process of synaptic plasticity, as well as in the long-term memory formation. Disruption of microRNA biogenesis leads to significant cognitive dysfunctions. Moreover, impaired microRNA biogenesis is one of the causes of the pathogenesis of mental disorders, neurodegenerative illnesses and senile dementia, which are often accompanied by deterioration in the learning ability and by memory impairment. Optimistic predictions are made that microRNAs can be used as targets for therapeutic treatment and for diagnosing the above pathologies. The importance of applications related to microRNAs significantly raises interest in studying their functions in the brain. Thus, this review is focused on the role of microRNAs in cognitive processes. It describes microRNA biogenesis and the role of miRNAs in the regulation of gene expression, as well as the latest achievements in studying the functional role of microRNAs in learning and in long-term memory formation, depending on the activation or inhibition of their expression. The review presents summarized data on the effect of impaired microRNA biogenesis on long-term memory formation, including those associated with sleep deprivation. In addition, analysis is provided of the current literature related to the prospects of improving cognitive processes by influencing microRNA biogenesis via the use of CRISPR/Cas9 technologies and active mental and physical exercises.Механизмы формирования долговременной памяти и способы ее улучшения (в случае нарушения) остаются сложнейшей нерешенной проблемой. В последние годы большое внимание в этой связи уделяется микроРНК. МикроРНК являются уникальными эндогенными некодирующими РНК длиной около 22 нуклеотидов, каждая из которых может регулировать трансляцию сотен матричных РНК, тем самым управляя целыми сетями генов. МикроРНК широко представлены в центральной нервной системе. В настоящее время значительное количество исследований посвящено изучению роли микроРНК в функционировании мозга. Показано, что целый ряд микроРНК вовлечен в процесс синаптической пластичности, а также в формирование долговременной памяти. При этом нарушение биогенеза микроРНК приводит к значительным когнитивным дисфункциям. Более того, нарушение биогенеза микроРНК является одной из причин патогенеза заболеваний, связанных с психическими расстройствами, нейродегенеративными патологиями и старческой деменцией, которые часто сопровождаются ухудшением способности к обучению и нарушением памяти. Высказываются оптимистичные прогнозы, что микроРНК могут быть использованы в качестве мишеней для терапевтического лечения и диагностики данных патологий. Важное прикладное значение микроРНК увеличивает интерес к изучению их функций в работе мозга. Представленный обзор посвящен роли микроРНК в когнитивных процессах. Описаны биогенез микроРНК и роль микроРНК в регуляции экспрессии генов. Рассмотрены последние достижения в изучении функциональной роли микроРНК в обучении и формировании долговременной памяти, в зависимости от активации или ингибирования их экспрессии, и о влиянии нарушения биогенеза микроРНК на формирование долговременной памяти. Небольшой раздел посвящен влиянию депривации сна на когнитивные процессы, зависимые от микроРНК. Кроме того, приведен анализ текущей литературы, связанной с перспективами улучшения когнитивных функций посредством влияния на биогенез микроРНК путем применения CRISPR/Cas9 технологий и активных умственных и физических нагрузок.

Increasing evidence indicates that exposure to inflammation during pregnancy intensifies the offspring’s cognitive impairment during aging, which might be correlated with changes in some synaptic plasticity-related proteins. In addition, an enriched environment (EE) can significantly exert a beneficial impact on cognition and synaptic plasticity. However, it is unclear whether gestational inflammation combined with postnatal EE affects the changes in cognition and synaptic plasticity-related proteins during aging. In this study, pregnant mice were intraperitoneally injected with lipopolysaccharides (LPS, 50 μg/kg) or normal saline at days 15–17 of pregnancy. At 21 days after delivery, some LPS-treated mice were randomly selected for EE treatment. At the age of 6 and 18 months, Morris water maze (MWM) and western blotting were, respectively, used to evaluate or measure the ability of spatial learning and memory and the levels of postsynaptic plasticity-related proteins in the hippocampus, including postsynaptic density protein 95 (PSD-95), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 subunit, and Homer-1b/c. The results showed that 18-month-old control mice had worse spatial learning and memory and lower levels of these synaptic plasticity-related proteins (PSD-95, GluA1, and Homer-1b/c) than the 6-month-old controls. Gestational LPS exposure exacerbated these age-related changes of cognition and synaptic proteins, but EE could alleviate the treatment effect of LPS. In addition, the performance during learning and memory periods in the MWM correlated with the hippocampal levels of PSD-95, GluA1, and Homer-1b/c. Our results suggested that gestational inflammation accelerated age-related cognitive impairment and the decline of PSD-95, GluA1, and Homer-1b/c protein expression, and postpartum EE could alleviate these changes.

Maternal malnutrition remains one of the major adversities affecting brain development and long-term mental health outcomes, increasing the risk to develop anxiety and depressive disorders. We have previously shown that malnutrition-induced anxiety-like behaviours can be rescued by a social and sensory stimulation (enriched environment) in male mice. Here, we expand these findings to adult female mice and profiled genome-wide ventral hippocampal 5hmC levels related to malnutrition-induced anxiety-like behaviours and their rescue by an enriched environment. This approach revealed 508 differentially hydroxymethylated genes associated with protein malnutrition and that several genes (N = 34) exhibited a restored 5hmC abundance to control levels following exposure to an enriched environment, including genes involved in neuronal functions like dendrite outgrowth, axon guidance, and maintenance of neuronal circuits (e.g. Fltr3, Itsn1, Lman1, Lsamp, Nav, and Ror1) and epigenetic mechanisms (e.g. Hdac9 and Dicer1). Sequence motif predictions indicated that 5hmC may be modulating the binding of transcription factors for several of these transcripts, suggesting a regulatory role for 5hmC in response to perinatal malnutrition and exposure to an enriched environment. Together, these findings establish a role for 5hmC in early-life malnutrition and reveal genes linked to malnutrition-induced anxious behaviours that are mitigated by an enriched environment.

Environmentally enriched housing conditions can increase performance on cognitive tasks in APP/PS1 mice; however, the potential effects of environmental enrichment (EE) on disease modification in terms of pathological change are inconclusive. We hypothesized that previous contrasting findings may be attributable to regional differences in susceptibility to amyloid beta (Aβ) plaque deposition in cortical regions that are functionally associated with EE. We characterized fibrillar plaque deposition in 6, 12, and 18-22 months old APP/PS1 mice in the prefrontal (PFC), somatosensory (SS2), and primary motor cortex (M1). We found a significant increase in plaque load between 6 and 12 months in all regions. In animals over 12 months, only the PFC region continued to significantly accumulate plaques. Additionally, 12 months old animals subjected to 6 months of EE showed improved spatial navigation and had significantly fewer plaques in M1 and SS2, but not in the PFC. These findings suggest that the PFC region is selectively susceptible to Aβ deposition and less responsive to the attenuating effects of EE. In contrast, M1 and SS2 regions plateau with respect to Aβ deposition by 12 months of age and are susceptible to amyloid pathology modification by midlife EE.

Environmental enrichment is a key component in improving the psychological and physiological well-being of animals under professional care. Environmental enrichment involves the addition of stimuli, including objects and cognitive challenges, into the environment in order to increase species-specific behaviour and provide opportunities for choice and control. The effectiveness of enrichment should be evaluated on a case-by-case basis to determine if the desired result has been achieved. Environmental enrichment devices (EEDs) can be utilised to present novel problems to animals under professional care. Here, a submerged interactive cognitive apparatus was presented to eight bottlenose dolphins (Tursiops truncatus) five days a week for 18 weeks and behavioural indicators of animal welfare assessed. As a group, dolphins spent more time in social swims compared to solitary swims and more time at the bottom of the habitat than the middle or top throughout the day, even when the apparatus was not immediately available. Individuals’ differences were apparent in the type and amount of engagement with the apparatus. Three dolphins engaged with the apparatus by solving it or consuming the reward. Two dolphins, D4 and D8, engaged simultaneously with the apparatus and participated in more social swimming with each other. D4 solved the interactive apparatus and engaged in more social active and solitary active behaviours. D1 and D4 increased their use of the bottom of the habitat. This study is the first report of underwater enrichment increasing dolphins time at depth throughout the day even when the enrichment device is not available. The interactive apparatus was an effective form of enrichment for dolphins participating in successful trials.

There is a growing ethical concern in modern society about animals' quality of life. We hypothesize that zoo visitors' perception of zoo animal welfare, particularly in the case of lesser anteaters, changes positively after listening to scientific information. Visitors observing active lesser anteaters in their enclosures at Córdoba Zoo (Argentina) were asked to respond to a questionnaire about animal welfare. The treatment group (T) answered the questionnaire after listening to a brief informative talk based on local scientific studies on lesser anteaters. The control group (C) answered the questionnaire without hearing the informative talk. Visitors (87.2%) considered biological, sanitary, and sociocultural aspects to be necessary conditions for optimum wild zoo-housed animal welfare. The majority of visitors considered that natural surroundings provide the highest level of welfare for wild animals. Visitors in the T group ranked the zoo as providing a higher level of animal welfare than those in group C. In reference to management measurements, the T group agreed on the positive effect of the application of environmental enrichment (Likert Medians: C = 4 and T = 5; p =.0443). On the basis of their perception, most visitors in both groups stated that the lesser anteaters at Córdoba Zoo appeared to be in a good state of welfare. We interpret this as meaning that, what these Córdoba zoo visitors personally perceived while observing the lesser anteaters carried greater weight than what they learned from the informative talk, though the talk did slightly affect their opinion., Fil: Chiapero, Florencia. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. CONICET. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina, Fil: Chiapero, Florencia. Jardín Zoológico Córdoba. CONICET. Laboratorio de Técnicas no Invasivas; Argentina, Fil: Ferrari, Ricardo H. Universidad Nacional de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina, Fil: Guglielmetti, Agustín. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias; Argentina, Fil: García Capocasa, María C. Jardín Zoológico Córdoba; Argentina, Fil: Busso, Juan M. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. CONICET. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina, Fil: Busso, Juan M. Jardín Zoológico Córdoba. CONICET. Laboratorio de Técnicas no Invasivas; Argentina, Fil: Busso, Juan M. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Ciencia y Tecnología de los Alimentos; Argentina

Although the use of fecal glucocorticoid metabolite (FGCM) measurements as non-invasive biomarkers for the stress response in mammals has increased, few studies have been conducted in odontocetes. We investigated if animal sex, age, pregnancy or contextual variations (season, sampling time, enrichment, social separation and presence of visitors) influenced the FGCM concentrations in presumably healthy, captive and endangered Yangtze finless porpoises (YFPs, N = 4) and bottlenose dolphins (BDs, N = 3). For YFPs, the FGCM concentrations were influenced by season (p = 0.01), diurnal variation (p = 0.01) and pregnancy (p = 0.005). Contextual variables that were associated with increases in FGCM concentrations included social separations (p = 0.003) and numbers of visitors (p = 0.0002). Concentrations of FGCMs were lower (p = 0.001) after exposure to environmental enrichment. For BDs, enrichment was associated with reduced concentrations of FGCMs (p &lt, 0.0001). The presence of visitors also influenced this species&rsquo, FGCM concentrations (p = 0.006). These results demonstrate that changes in the FGCM concentrations in YFPs and BDs may occur in response to contextual and social changes. In combination with other behavioral and physiological assessments, measurements of FGCMs may be a useful tool for monitoring cetacean welfare. Such monitoring may help researchers identify and better understand situations that may be stressful for animals and, therefore, improve management and husbandry. Furthermore, results from our study and inferences of the FGCM concentrations in cetaceans, and their potential relationship to stress, may be extrapolated to studies of free-ranging animals, which may help detect possible environmental or anthropogenic stressors that could be affecting these populations.

Adverse early life experiences are major influences on developmental trajectories with potentially life-long consequences. Prenatal or early postnatal exposure to stress, undernutrition or environmental toxicants may reprogram brain development and increase risk of behavioural and neurological disorders later in life. Not only experience within a single lifetime, but also ancestral experience affects health trajectories and chances of successful aging. The central mechanism in transgenerational programming of a disease may be the formation of epigenetic memory. This review explores transgenerational effects of early adverse experience on health and disease incidence in older age. First, we address mechanisms of developmental and transgenerational programming of disease and inheritance. Second, we discuss experimental and clinical findings linking early environmental determinants to adverse aging trajectories in association with possible parental contributions and sex-specific effects. Third, we outline the main mechanisms of age-related functional decline and suggest potential interventions to reverse negative effects of transgenerational programming. Thus, strategies that support healthy development and successful aging should take into account the potential influences of transgenerational inheritance.

The sigma-1 receptor (S1R) is a membrane-associated protein expressed in neurons and glia at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs). S1R interacts with different partners to regulate cellular responses, including ER stress, mitochondrial physiology and Ca2+ fluxes. S1R shapes cellular plasticity by directly modulating signaling pathways involved in inflammatory responses, cell survival and death. We here analyzed its impact on brain plasticity in vivo, in mice trained in a complex maze, the Hamlet test. The device, providing strong enriched environment (EE) conditions, mimics a small village. It has a central agora and streets expanding from it, leading to functionalized houses where animals can Drink, Eat, Hide, Run, or Interact. Animals were trained in groups, 4 h/day for two weeks, and their maze exploration and topographic memory could be analyzed. Several groups of mice were considered: non-trained vs. trained; repeatedly administered with saline vs. NE-100, a selective S1R antagonist; and wildtype vs. S1R KO mice. S1R inactivation altered maze exploration and prevented topographic learning. EE induced a strong plasticity measured through resilience to behavioral despair or to the amnesic effects of scopolamine, and increases in S1R expression and bdnf mRNA levels in the hippocampus; increases in neurogenesis (proliferation and maturation); and increases of histone acetylation in the hippocampus and cortex. S1R inactivation altered all these parameters significantly, showing that S1R activity plays a major role in physiological brain plasticity. As S1R is a major resident protein in MAMs, modulating ER responses and mitochondrial homeostasy, MAM physiology appeared impacted by enriched environment.

There are more captive tigers in the United States than there are wild tigers in the entire world. Many animals under human care engage in problem behaviors such as excessive grooming and aggression, although the origin of these behaviors is typically unknown. Environmental enrichment may mitigate these issues in captive animals of all kinds. In order to individualize enrichment experiences, the current study used a free-operant assessment procedure to establish a menu of most preferred play items and scents among 7 Bengal tigers (Panthera tigris tigris) housed at a sanctuary in southwest Missouri. Each tiger was tested 3 times with scents (cinnamon and Calvin Klein Obsession perfume) and play items (boxes, balls, leaves, and pumpkins). The importance of rigorous assessment of presumed reinforcers among captive wild animals, as well as the difficulty of effectively assessing tigers while ensuring the safety of both the participants and researchers, is discussed.

Social and environmental factors impact cancer and energy balance profoundly. Years ago, our lab established the existence of a novel brain-fat interaction we termed the "hypothalamic-sympathoneural-adipocyte (HSA) axis", through which complex environmental stimuli provided by an enriched environment regulate body composition, energy balance, and development of cancer. We have spent a significant portion of the past decade to further characterize the broad health benefits of an enriched environment (for example, leanness, enhanced immune function, and cancer resistance), and to identify mediators in the brain and periphery along the HSA axis. This review summarizes our recent work regarding the interface between endocrinology, immunology, cancer biology, aging, and neuroscience. We will discuss the interplay between these systemic phenomena and how the HSA axis can be targeted for regulation of cancer and aging.

Environmental enrichment is an important tool utilized to improve animal welfare in zoological institutions through opportunity for mental and physical stimulation. Many past studies have focused on the impact enrichment has on animal behavior; however, none have conducted preference assessments on enrichment items to examine the relationship between animals' preferences and interaction with enrichment over a 24-hr period. Ten-minute free operant, paired-choice preference assessments were implemented in Study 1 to determine the enrichment preferences of African lions (N = 3). Following Study 1, Study 2 was conducted, which examined the behavior of African lions with enrichment items over the course of 30, 24-hr trials to evaluate the relationship between preferences established in Study 1 and long-term interaction with the enrichment. Generalized estimating equations revealed a statistically significant relationship between the percentage of time the enrichment was approached first and the average duration of interaction in Study 1 to the total duration of interaction and the percent of hours interacted with the item in Study 2. Additionally, the first 2 min of the preference data resulted in comparable statistically significant findings, demonstrating shorter preference assessments can produce similar results. The results support our prediction that preference assessments can be used to estimate the amount of interaction with enrichment over the course of time, with preferred items being interacted with more frequently and in longer duration. Information gained from this study suggests preference assessments can be a time and cost-effective tool to evaluate enrichment preference and predicted efficacy.