Enriched Environment Treatment Research Articles

Effects of the provision of a hiding box or shelf on the behaviour and faecal glucocorticoid metabolites of bold and shy cats housed in single cages

It is often stressful for cats to be placed in cages in a shelter and environmental enrichment (EE) of the caging is one mechanism for mitigating this stress. The behavioural style of 72 cats was assessed as bold or shy. They were then randomly allocated (approximately balanced by behavioural style) to one of the following EE treatments in single standard cages: a hiding box (BOX), a perching shelf (SHELF), or no additional EE (CTRL) and their behavioural and faecal glucocorticoid metabolite (FGM) responses were examined. Continuous focal observations of activity, location in the cage, and posture were conducted using video recordings of two 4-h periods/day/cat, over a period of 10 days. Food intake and Cat-Stress-Scores (CSS) were recorded daily. Faecal samples were collected for analysis of FGM. The data were analysed using repeated measures models with fixed effects of day, treatment group, behavioural style, and their interactions. Cats in BOX had significantly lower FGM, and consumed significantly more food daily, than did cats in CTRL. Shy cats had a significantly greater probability of registering a CSS ≥ 3 and had a significantly greater CSS on days 1–3 than bold cats, and within the treatment group BOX, shy cats spent a significantly greater percentage of time in the hiding box than bold cats. Day in study was a significant factor for daily food intake and percentage of time spent eating – which tended to increase across time – and for percentage of time spent grooming – which tended to decrease across time. These results suggest that the caging was a stressor that was partially mitigated by the inclusion of EE (a hiding box), that the stress responses of bold and shy cats differed, and that the stress diminishes with time. The results confirm the benefit of the provision of a hiding box in singly housed caging.

Environmental enrichment combined with fasudil promotes motor function recovery and axonal regeneration after stroke.

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.

Effects of Gestational Inflammation with Postpartum Enriched Environment on Age-Related Changes in Cognition and Hippocampal Synaptic Plasticity-Related Proteins

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.

Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy.

Autophagy is crucial for maintaining cellular homeostasis, and can be activated after ischemic stroke. It also participates in nerve injury and repair. The purpose of this study was to investigate whether an enriched environment has neuroprotective effects through affecting autophagy. A Sprague-Dawley rat model of transient ischemic stroke was prepared by occlusion of the middle cerebral artery followed by reperfusion. One week after surgery, these rats were raised in either a standard environment or an enriched environment for 4 successive weeks. The enriched environment increased Beclin-1 expression and the LC3-II/LC3-I ratio in the autophagy/lysosomal pathway in the penumbra of middle cerebral artery-occluded rats. Enriched environment-induced elevations in autophagic activity were mainly observed in neurons. Enriched environment treatment also promoted the fusion of autophagosomes with lysosomes, enhanced the lysosomal activities of lysosomal-associated membrane protein 1, cathepsin B, and cathepsin D, and reduced the expression of ubiquitin and p62. After 4 weeks of enriched environment treatment, neurological deficits and neuronal death caused by middle cerebral artery occlusion/reperfusion were significantly alleviated, and infarct volume was significantly reduced. These findings suggest that neuronal autophagy is likely the neuroprotective mechanism by which an enriched environment promotes recovery from ischemic stroke. This study was approved by the Animal Ethics Committee of the Kunming University of Science and Technology, China (approval No. 5301002013855) on March 1, 2019.

Improvement of autophagy dysfunction as a potential mechanism for environmental enrichment to protect blood-brain barrier in rats with vascular cognitive impairment

Vascular cognitive impairment (VCI) is the second most common cause of dementia after Alzheimer’s disease, and the cognitive impairment is one of the common effects of VCI. Unfortunately, it lacks effective therapeutic treatments at present. In our previous study, environmental enrichment (EE), as an early intervention for lifestyle modification, can ameliorate cognitive impairment by attenuating hippocampal blood-brain barrier (BBB) injury in chronic cerebral hypoperfusion (CCH) rats. However, the underlying mechanism remains unclear. Here, we found CCH rats in the standard environment (SE) developed cognitive impairment and BBB damage, which were significantly alleviated with the EE intervention. Meantime, EE improved the autophagy dysfunction caused by CCH in the hippocampus of rats, suggesting that the effect of EE on cognitive function and BBB may be related to the improvement of autophagy pathway.

Postweaning Enriched Environment Enhances Cognitive Function and Brain-Derived Neurotrophic Factor Signaling in the Hippocampus in Maternally Separated Rats

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.

The three-phase enriched environment paradigm promotes neurovascular restorative and prevents learning impairment after ischemic stroke in rats

Enriched environment (EE) with a complex combination of sensorimotor, cognitive and social stimulations has been shown to enhance brain plasticity and improve recovery of functions in animal models of stroke. The present study extended these findings by assessing whether the three-phase EE intervention paradigm would improve neurovascular remodeling following ischemic stroke.Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). A three-phase EE intervention paradigm was designed in terms of the different periods of cerebral ischemia by periodically rearranging the EE cage. Morris water maze (MWM) tests were performed to evaluate the learning and memory function. Multimodal MRI was applied to examine alterations to brain structures, intracranial vessels, and cerebral perfusion on the 31st day after MCAO. The changes of capillaries ultrastructure were examined by transmission electron microscope. Double-immunofluorescent staining was used to evaluate neurogenesis and angiogenesis. The expression of angiogenesis-related factors and neurovascular remodeling related signaling pathways including Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/β-catenin and the axon guidance molecules were detected by Western blot analysis.MRI measurements revealed that EE treatment significantly increased survival volume of cortex and striatum, improved cerebral blood flow (CBF), amplified anterior azygos cerebral artery (azACA), ipsilateral internal carotid artery (ICA) and anterior communicating artery (AComA) vessel signal compared with standard housed rats (IS). Consistent with these findings, EE reduced ischemic BBB damage of capillary, enhanced endogenous angiogenesis and modified the expression of VEGF, Ang-1 or Ang-2 in ischemic rats. Additionally, this proangiogenic effect was consistent with the increased progenitor cell proliferation and neuronal differentiation in the peri-infarct cortex and striatum after EE intervention. Specifically, EE intervention paradigm markedly increased expression of phosphorylated PI3K, AKT and GSK-3, but reduced phosphorylated β-catenin. Moreover, the axon guidance proteins expression level was significant higher in EE group. In parallel to these findings, EE significantly enhanced recovery of lost spatial learning memory function in MCAO rats without affecting infarct size.Together, MRI findings along with histological results strongly supported that the three-phase EE paradigm benefited neurovascular reorganization and thereby improved poststroke cognitive function. Moreover, our findings suggest that this type of EE paradigm induced neurogenesis and angiogenesis, at least in part, via regulating PI3K/AKT/GSK-3/β-catenin signaling pathway and activation of the intrinsic axonal guidance molecules in animal models of ischemic stroke.

The Effects of Sensory Enrichment After a Laboratory Stressor on Human Skin Barrier Recovery in a Randomized Trial.

Environmental enrichment (EE) can reduce stress, alter immunity, and speed wound healing in animals. However, it is not known whether these effects translate to humans. This study aimed to investigate whether sensory EE could improve wound healing after a stressor in humans. A total of 105 participants underwent a tape-stripping procedure and were then stressed using a laboratory stress paradigm. After this, they were randomized to interact for 30 minutes with one of two possible sensory EE interventions (music as auditory enrichment or a Paro robot as multisensory enrichment) or to a control condition. Skin barrier recovery was measured using transepidermal water loss at baseline, after the stressor, and after the intervention. Stress was measured using self-report, heart rate, blood pressure, and salivary stress-related biological measures. Enjoyment during the intervention was measured by self-report as a possible mediator. The Paro condition had significantly improved skin barrier recovery (mean [M] = 44%, standard error [SE] = 1.92) compared with the control condition (M = 37% SE = 2.01, F(2,88) = 3.25, p = .043), both with and without controlling for covariates. The music condition did not significantly differ from the other conditions (M = 42%, SE = 1.95, p values > .05). Both objective and subjective stress measures did not significantly differ between conditions. Mediational analysis showed that enjoyment levels during the intervention period significantly mediated the relationship between condition and skin barrier recovery (z = 2.00, p = .046). Paro, or other companion robots, may be an effective form of enrichment to improve skin barrier recovery in humans after a laboratory stressor, and this effect may be due to enjoyment. Further research with patient groups is required to investigate whether Paro can help heal clinical wounds. ACTRN12618000953235, registered at https://anzctr.org.au.

Simultaneous Monitoring of Wireless Electrophysiology and Memory Behavioral Test as a Tool to Study Hippocampal Neurogenesis.

Brainwaves amplitude obtained from electroencephalography (EEG) has been well-recognized as a basis for cognitive capacity, memory, and learning on animals and humans. Adult neurogenesis mechanism is also linked to memory and learning improvement. Traditionally, researchers used to assess learning and memory parameters in rodent models by behavioral tasks. Therefore, the simultaneous monitoring of behavioral changes and EEG is particularly interesting in correlating data between brain activity and task-related behaviors. However, most of the equipment required to perform both studies are either complex, expensive, or uses a wired setup network that hinders the natural animals' movement. In this study, EEG was recorded with a wireless electrophysiology device along with the execution of a novel object recognition task (NORT). The animal's behavior was monitored simultaneously by a video tracking system. Both recordings were analyzed offline by their timestamps which were synched to link EEG signals with the animal's actions. Subjects consist of adult Wistar rats after medium-term environmental enrichment treatment. Six skull screw electrodes were fixed in pairs on both hemispheres over frontal, central, and parietal regions and were referenced to an electrode located posterior of the nasal bone. NORT protocol consists of exposing the animal to two identical objects for 10 min. After 2 h and 24 h, one of the objects was replaced with a novel one. Exploration time for each object was monitored by a behavioral tracking software (BTS) and EEG data recording. The analysis of the EEG synced with behavioral data consists of estimations of alpha and beta relative band power and comparisons between novel object recognition versus familiar object exploration, between three experimental stages. In this manuscript, we have discussed electrodes manufacturing process, epidural electrodes implantation surgery, environmental enrichment protocol, NORT protocol, BTS setup, EEG - BTS coupling for simultaneous monitoring in real-time, and EEG data analysis based on automatic events detection.

Implementing environmental enrichment strategies to help children who have sustained a moderate or severe traumatic brain injury

Every year in the UK, a significant number of children sustain a moderate or severe traumatic brain injury (TBI). Children who sustain a moderate or severe TBI have been shown to experience continuing neurological decline in two or more domains up to five years post‐injury. Environmental enrichment (EE)—which involves supplementing an environment with appropriately reinforced and rewarded, frequently changing, novel experiences—has been shown to effectively improve social and cognitive functioning in animals with experimental TBI. A growing body of evidence shows EE is also beneficial in the recovery of humans following a TBI. Children who have sustained a moderate or severe TBI often return to school and the educational setting is well‐suited for the implementation of EE interventions during the later stages of TBI recovery. This paper reviews a variety of factors pertinent to moderate and severe TBI, neurorehabilitation and EE. It also offers EE considerations for educational professionals who are involved in the development and implementation of school‐based interventions for children who have sustained a significant brain injury.

Enhanced white matter reorganization and activated brain glucose metabolism by enriched environment following ischemic stroke: Micro PET/CT and MRI study

Enriched environment (EE) is an effective rehabilitative protocol designed to enhance sensorimotor, cognitive and social stimulation. Current understanding of neuronal remodeling after EE intervention mainly derived from conventional histological methods. The efficacy of EE treatment on post-stroke brain reorganization still needed to be elucidated in vivo. This study aimed to examine the effects of post-ischemic EE treatment on the brain remodeling using magnetic resonance imaging (MRI) and 18F-FDG positron emission tomography (PET). Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and housed in standard environment (SE) or EE for consecutive 30 days. Cognitive testing was performed using the Morris water maze. White matter structural modifications were detected by MRI combined with histological analysis. In addition, PET scanning with 18F-FDG as a molecular probe was conducted to detect brain energy metabolism. Our results showed that EE significantly mitigated MCAO-induced impairments in spatial learning and memory, attenuated brain atrophy, protected white matter integrity, and enhanced white matter reorganization coupled with promoting oligodendrogenesis. In parallel to these findings, PET-MRI fused images showed that EE remarkably elevated regional cerebral metabolic rates of glucose in the lesioned sensorimotor cortex, striatum and corpus callosum/external capsule. More importantly, a strong correlation was demonstrated between glucose utilization and diffusion tensor imaging indices in the corresponding brain regions. The data herein indicated that improved global metabolism of glucose was a critical step in the reorganization of the white matter following post-stroke EE intervention. Although EE did not produce beneficial effects on restoring brain infarct volume, the broad range of structural and functional benefits observed in the present study raised the interesting possibility that EE might be an effective rehabilitative strategy for ischemic stroke.

The effects of environmental enrichment on skin barrier recovery in humans: a randomised trial

This study investigated whether environmental enrichment (EE) could reduce stress and improve wound healing in humans. 120 participants underwent a standardised tape-stripping procedure and were then randomised to interact for 30 minutes with one of three EE interventions (comfort blankets as tactile enrichment, music as auditory enrichment or a Paro robot as multi-sensory enrichment) or to a control group. Skin barrier recovery (SBR) was measured using transepidermal water loss at baseline, after tape-stripping and after the intervention. Psychological variables, cortisol and alpha-amylase were measured at the three time-points. SBR did not significantly differ between the EE conditions and the control condition. The music condition had higher stimulation levels than the control condition, and the comfort condition had significantly lower relaxation levels than the control condition after the intervention. The EE interventions tested were not beneficial for wound healing compared to a control group. Limitations were that the sample were not stressed and an active control condition was used.

BDNF deficiency and enriched environment treatment affect neurotransmitter gene expression differently across ages.

Deficiency of activity-induced expression of brain-derived neurotrophic factor (BDNF) disturbs neurotransmitter gene expression. Enriched environment treatment (EET) ameliorates the defects. However, how BDNF deficiency and EET affect the neurotransmitter gene expression differently across ages remains unclear. We addressed this question by determining the neurotransmitter gene expression across three life stages in wild-type and activity-dependent BDNF-deficient (KIV) mice. Mice received 2-months of standard control treatment (SCT) or EET at early-life development (ED: 0-2months), young adulthood (2-4months), and old adulthood (12-14months) (N=16/group). Half of these mice received additional 1-month SCT to examine persisting EET effects. High-throughput quantitative reverse transcription polymerase chain reaction measured expression of 81 genes for dopamine, adrenaline, serotonin, gamma aminobutyric acid, glutamate, acetylcholine, and BDNF systems in the frontal cortex (FC) and hippocampus. Results revealed that BDNF deficiency mostly reduced neurotransmitter gene expression, greatest at ED in the FC. EET increased expression of a larger number of genes at ED than adulthood, particularly in the KIV FC. Many genes down-regulated in KIV mice were up-regulated by EET, which persisted when EET was provided at ED (e.g., 5-hydroxytryptamine (serotonin) transporter [5HTT], ADRA1D, GRIA3, GABRA5, GABBR2). In both the regions, BDNF deficiency decreased the density of gene co-expression network specifically at ED, while EET increased the density and hub genes (e.g., GAT1, GABRG3, GRIN1, CHRNA7). These results suggest that BDNF deficiency, which occurs under chronic stress, causes neurotransmitter dysregulations prominently at ED, particularly in the FC. EET at ED may be most effective to normalize the dysregulations, providing persisting effects later in life. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. More information about the Open Science badges can be found at https://cos.io/our-services/open-science-badges/.

Effects of environmental enrichment on growth performance, aggressive behavior and stress-induced changes in cortisol release and neurogenesis of black rockfish Sebastes schlegelii

Fish welfare and behavioral flexibility in aquaculture have gained increasing concern among scientists and the public. Stress-related behavioral and physiological responses and neural plasticity are important aspects of fish welfare. Recently, environmental enrichment has been regarded as a promising way to promote fish growth, decrease aggression, and enhance behavioral flexibility; however, relatively few studies focusing on the effects of enrichment and stress on fish neural plasticity have been conducted. In this work, we tested the main and interaction effects of physical enrichment (rearing for eight weeks) and/or acute stress (air exposure and confinement) on the growth performance, aggressive behavior, stress response, and brain expression levels of genes involved in neurogenesis (i.e., proliferating cell nuclear antigen, doublecortin and neuronal differentiation factor; pcna, dcx and neurod, respectively) of juvenile black rockfish Sebastes schlegelii. In general, environmental enrichment treatment significantly decreased fish aggressive behavior and the levels of basal cortisol, while it enhanced the gene expression levels of pcna and dcx in the brain. As expected, the fish exposed to acute stress had significantly higher levels of cortisol and brain pcna gene expression compared with fish at a basal status. Enrichment and stress had significant interaction effect on fish cortisol levels. Furthermore, statistically significant correlations (P < .05) between aggressive behavior and stress response (indicated by cortisol level) and between cortisol and neurogenesis biomarkers (especially pcna) were observed. The growth performance of the enriched fish was statistically similar to that of the barren-reared fish. No main or interaction effect of enrichment and stress on brain neurod gene expression was detected. This is the first evidence showing that environmental enrichment and acute stress can produce significant effects on processes of fish neurogenesis. These findings confirm the positive effects of environmental enrichment on fish stress responses and neurogenesis in the context of acute stress, which may lay the foundation for improved welfare and behavioral flexibility of fish in the aquaculture industry.

Impact of a cattle brush on feedlot steer behavior, productivity and stress physiology

The aim of the present study was to investigate the impact of environmental enrichment (EE), in the form of a cattle brush, on feedlot cattle behavior, productivity and stress physiology. Steers were blocked by weight and assigned to one of two treatments 1) Cattle brush secured to fence line (BRUSH; n = 3 pens; 25 animals) or 2) No enrichment (CON; n = 3 pens; 26 animals). Video recordings were decoded from 0800 to 1730 on d -2, -1, 0, 1, 2, 4, 8, 16, 32 and 64 relative to brush implementation. Headbutting, kicking, mounting, bar licking, tongue rolling, allogrooming and brush usage were scored through continuous observation. Scan samples at 10-minute intervals were utilized to score lying, drinking and eating. Rumination and activity data were collected from rumination collars. Hair coat shed scores were recorded upon feedlot arrival (d -55) and prior to first block slaughter shipment (d 161). Body weights and hair samples for cortisol extraction were obtained at 35 d intervals. Performance measures were calculated weekly and carcass data were collected at slaughter. Impact of day, treatment, and their interaction on cattle behavior and physiological measures and the impact of treatment on performance measures was evaluated in SAS.Cattle housed in BRUSH pens performed fewer headbutts (P = 0.013) over time compared to CON cattle. For BRUSH cattle, frequency and duration of brush usage changed over time, peaking on d 0 (P < 0.01). Environmental enrichment treatment impacted mounting, bar licking, tongue rolling, allogrooming and activity levels (P < 0.05). Cattle housed in BRUSH pens engaged in fewer mounts, bar licking bouts, tongue rolling bouts and allogrooming bouts and performed all behaviors for a shorter duration of time compared to CON cattle. Research day impacted mounting, bar licking, tongue rolling, allogrooming, activity and rumination (P < 0.05). Mounting frequency, bar licking frequency, bar licking duration, activity duration and rumination duration decreased over time while frequency and duration of tongue rolling and allogrooming increased over time. A smaller proportion of steers were observed lying on d 0 and d 4 (P = 0.001) and the proportion of steers feeding decreased over time (P = 0.04). Cattle assigned to BRUSH pens performed fewer stereotypic and aggressive behaviors and cattle did not habituate to the brush suggesting that a cattle brush could provide a lasting benefit to feedlot cattle.

Environmental enrichment enhances post-ischemic cerebral blood flow and functional hyperemia in the ipsilesional somatosensory cortex

Environmental enrichment has been reported to promote functional recovery in an ischemic stroke. However, the underlying mechanism remains unclear. This study aimed to investigate the effect of environmental enrichment treatment on post-ischemic cerebral blood flow and functional hyperemia in the ipsilesional primary somatosensory cortex of rats. With laser speckle imaging, we were able to monitor the resting cerebral blood flow alteration in the middle cerebral artery occlusion model. Both 3- and 28-day post-ischemic infarct volumes were then examined with triphenyltetrazolium chloride and cresyl violet staining, respectively. We found that an exposure to environmental enrichment was associated with higher post-ischemic cerebral blood flow and less brain tissue loss in the ipsilesional primary somatosensory cortex compared with the standard cage environment. Furthermore, environmental enrichment also enhanced the cerebral blood flow response to whisker stimulation in the ipsilesional barrel cortex when measured 28 days after the middle cerebral artery occlusion. Together, the data suggested that an exposure to environmental enrichment promoted the restoration of cerebral blood flow in the ipsilesional cortex and contributed to a better coupling between functional activation and cerebral blood flow change, which might be the possible mechanisms underlying the neuroprotective effects of EE after ischemia.

Mapping accumulative whole-brain activities during environmental enrichment with manganese-enhanced magnetic resonance imaging

An enriched environment (EE) provides multi-dimensional stimuli to the brain. EE exposure for days to months induces functional and structural neuroplasticity. In this study, manganese-enhanced magnetic resonance imaging (MEMRI) was used to map the accumulative whole-brain activities associated with a 7-day EE exposure in freely-moving adult male mice, followed by c-Fos immunochemical assessments. Relative to the mice residing in a standard environment (SE), the mice subjected to EE treatment had significantly enhanced regional MEMRI signal intensities in the prefrontal cortex, somatosensory cortices, basal ganglia, amygdala, motor thalamus, lateral hypothalamus, ventral hippocampus and midbrain dopaminergic areas at the end of the 7-day exposure, likely attributing to enhanced Mn2+ uptake/transport associated with brain activities at both the regional and macroscale network levels. Some of, but not all, the brain regions in the EE-treated mice showing enhanced MEMRI signal intensity had accompanying increases in c-Fos expression. The EE-treated mice were also found to have significantly increased overall amount of food consumption, decreased body weight gain and upregulated tyrosine hydroxylase (TH) expression in the midbrain dopaminergic areas. Taken together, these results demonstrated that the 7-day EE exposure was associated with elevated cumulative activities in the nigrostriatal, mesolimbic and corticostriatal circuits underpinning reward, motivation, cognition, motor control and appetite regulation. Such accumulative activities might have served as the substrate of EE-related neuroplasticity and the beneficial effects of EE treatment on neurological/psychiatric conditions including drug addiction, Parkinson’s disease and eating disorder.

Effect of environmental enrichment on weaned piglets: physiological responses

The aim of this research consisted in assessing the effect of various kinds of environmental enrichment (EE) on the physiological responses of weaned piglets. The mean age of the 96 piglets that participated was 27 days. The piglets were weaned and then housed under two conditions: with no disruption of the social order (SO), and with disruption of the social order (DSO). After establishing the two experimental conditions, we proceeded to evaluate four different treatments; namely, control (C), suspended ropes (SR), aromatized bottles (AB) and pet toys and balls (PTB). The protocol required drawing three blood samples: at 30 (T&lt;sub&gt;30&lt;/sub&gt;), 60 (T&lt;sub&gt;60&lt;/sub&gt;) and 90 min (T&lt;sub&gt;90&lt;/sub&gt;) after weaning. The DSO piglets had higher pH and haematocrit levels than those weaned in the SO condition (P &amp;lt; 0.05). Also, pCO&lt;sub&gt;2&lt;/sub&gt;, potassium (K&lt;sup&gt;+&lt;/sup&gt;) and base excess (BE) concentrations were higher in the SO animals than in those in the DSO group (P &amp;lt; 0.05). The control piglets, which did not receive any type of EE, showed higher pCO&lt;sub&gt;2&lt;/sub&gt; levels, but lower glucose and pH (P &amp;lt; 0.05) values, while the ones enriched with SR had increased lactate levels, but lower values for pH and HCO&lt;sub&gt;3&lt;/sub&gt;&lt;sub&gt;–&lt;/sub&gt; compared to the piglets in the other EE treatment regimens (P &amp;lt; 0.05). The SR-enriched piglets had higher lactate and haematocrit levels, but lower values for pH and bicarbonate (HCO&lt;sub&gt;3&lt;/sub&gt;&lt;sub&gt;–&lt;/sub&gt;) than the animals in the other EE groups (P &amp;lt; 0.005). The piglets subjected to sensorial EE with AB had higher plasma glucose than the ones in the other groups (P &amp;lt; 0.005). Finally, the PTB-enriched subjects showed higher Na&lt;sup&gt;+ &lt;/sup&gt;levels than controls (P &amp;lt; 0.005). The alterations that were found to be related to the factor sampling time were more pronounced at T&lt;sub&gt;30&lt;/sub&gt; (P &amp;lt; 0.05) than T&lt;sub&gt;60&lt;/sub&gt; and T&lt;sub&gt;90&lt;/sub&gt;. These results indicate that the conditions (SO, DSO) and EE (C, SR, AB, PTB) under which the piglets were weaned influenced the blood variables measured in the study.

Environmental Enrichment and Brain Neuroplasticity in the Kainate Rat Model of Temporal Lobe Epilepsy.

Background and PurposeEnvironmental enrichment (EE) improves brain function and ameliorates cognitive impairments; however, whether EE can reverse the learning and memory deficits seen following seizures remains unknown.MethodsWe tested the hypothesis that EE augments neurogenesis and attenuates the learning and memory deficits in rats subjected to kainate-induced seizures in hippocampus, amygdala and motor cortex. EE consisted of daily exposures immediately after KA lesioning (early EE) and after a 60-day period (late EE). Morphometric counting of neuron numbers (NN), dendritic branch-points and intersections (DDBPI) were performed. Spatial learning in a T-maze test was described as percent correct responses and memory in a passive-avoidance test was calculated as time spent in the small compartment where they were previously exposed to an aversive stimulus.ResultsEE increased NN and DDBPI in the normal control and in the KA-lesioned rats in all brain areas studied, after both early and late exposure to EE. Late EE resulted in significantly fewer surviving neurons than early EE in all brain areas (p < 0.0001). EE increased the percent correct responses and decreased time spent in the small compartment, after both early and late EE. The timing of EE (early vs. late) had no effect on the behavioral measurements.ConclusionsThese findings demonstrate that, after temporal lobe and motor cortex epileptic seizures in rats, EE improves neural plasticity in areas of the brain involved with emotional regulation and motor coordination, even if the EE treatment is delayed for 60 days. Future studies should determine whether EE is a useful therapeutic strategy for patients affected by seizures.

Handling has an anxiolytic effect that is not affected by the inhibition of the protein kinase C pathway in adult prenatal undernourished male rat offspring.

Environmental enrichment (EE) after birth has been reported as an intervention improving the anxiety-like behavior and cognitive deficit due to maternal restraint, foot-shock, or social stress during pregnancy. However, it remains unclear whether EE after birth could benefit the early prenatal undernourished offspring. In this study, we examined the effect of daily handling as a simple EE intervention on the aberrant behavior of prenatally undernourished rats. The male rat offspring exhibited anxiety-like behavior at 9 weeks of age due to maternal food restriction in early pregnancy. Our study shows that the daily handling after weaning has an anxiolytic effect in the prenatally undernourished offspring without affecting the behavior of prenatally well-nourished offspring. Conversely, the concentrations of dopamine, serotonin, norepinephrine, and their metabolites were not altered in the prefrontal cortex by prenatal undernutrition or daily handling after weaning. We investigated whether the anxiolytic effect of daily handling was mediated by the protein kinase C (PKC) pathway using the PKC inhibitor, chelerythrine. The anxiolytic effect of the handling was not canceled by chelerythrine injection in prenatally undernourished offspring, whereas chelerythrine induced an anxiety-like behavior in control rats. Our results suggest that maternal undernutrition in early pregnancy induces an anxiety-like behavior accompanied with a PKC pathway-hyporesponsiveness; however, daily handling ameliorates the anxiety-like behavior through a PKC-independent pathway.