Continuous Environmental Enrichment Research Articles

Sex difference in cognitive behavioral alterations and barrel cortex neuronal responses in rats exposed prenatally to valproic acid under continuous environmental enrichment.

Autism spectrum disorder is a developmental disorder that can affect social interactions and sensory-motor behaviors. The present study investigates the effect of environmental enrichment (EE) on behavioral alterations and neuron responses associated with the barrel cortex of young adult female and male rats exposed prenatally to valproic acid (VPA). Pregnant female rats were pretreated with either saline or VPA (500 mg/kg, IP) on day 12.5 of gestation. Male and female pups were exposed to either EE or standard-setting (non-enrichment) conditions for 1 month (between postnatal day [PND] 30 and 63-65) and were divided into non-EE (control), EE, VPA, and VPA + EE groups. Three-chamber sociability and social novelty, acoustic startle reflex, and texture discrimination tests were conducted on PND 62. Responses of barrel cortex neurons of male pups were evaluated using the extracellular single-unit recording technique on PND 63-65. Results showed that the performance of rats of both sexes in social interactions, texture discrimination tasks, and acoustic startle reflex significantly decreased in the VPA groups compared with the control rats (P <0.05). In this regard, EE attenuated the altered deficit performance observed in the VPA animals compared with the VPA-EE animals (P <0.05). The performance of females was better than males in the discrimination tasks and acoustic startle reflex. In contrast, males were better than females in the three-chamber social interaction test. Additionally, the excitatory receptive field response magnitude of the barrel cortex neurons in the VPA + EE group increased compared with the VPA group (P <0.05). The results suggest that continuous EE can attenuate cognitive function disturbances in autistic-like rats and, at least at the behavioral level, the effects depend on sex.

Prolonged Environmental Enrichment Promotes Developmental Myelination.

Postnatal neurodevelopment is profoundly influenced by environmental experiences. Environmental enrichment is a commonly used experimental paradigm that has uncovered numerous examples of experience-dependent plasticity in health and disease. However, the role of environmental enrichment in normal development, especially glial development, is largely unexplored. Oligodendrocytes, the myelin-forming glia in the central nervous system, provide metabolic support to axons and establish efficient saltatory conduction by producing myelin. Indeed, alterations in myelin are strongly correlated with sensory, cognitive, and motor function. The timing of developmental myelination is uniquely positioned to be influenced by environmental stimuli, as peak myelination occurs postnatally and continues into adulthood. To determine if developmental myelination is impacted by environmental experience, mice were housed in an enriched environment during peak myelination through early adulthood. Using translating ribosome affinity purification, oligodendrocyte-specific RNAs were isolated from subcortical white matter at various postnatal ages. RNA-sequencing revealed that differences in the oligodendrocyte translatome were predominantly evident after prolonged and continuous environmental enrichment. These translational changes corresponded with altered oligodendrocyte lineage cell dynamics and enhanced myelination. Furthermore, consistent with increased developmental myelination, enriched mice displayed enhanced motor coordination on a beam walking task. These findings indicate that protracted environmental stimulation is sufficient to modulate developmental myelination and to promote behavioral function.

Effect of environmental enrichment for piglets in the nursery phase.

ObjectiveThe effect of environmental enrichment on the behaviour of piglets in the nursery phase was evaluated.MethodsA 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.ResultsA 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.ConclusionThe 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.

Neurobehavioral Effects of Restricted and Unpredictable Environmental Enrichment in Rats.

To study how motivational factors modulate experience-dependent neurobehavioral plasticity, we modify a protocol of environmental enrichment (EE) in rats. We assumed that the benefits derived from EE might vary according to the level of incentive salience attributed to it. To enhance the rewarding properties of EE, access to the EE cage varied randomly from 2 to 48 h for 30 days (REE). The REE group was enriched only 50% of the time and was compared to standard housing and continuous EE (CEE) groups. As behavioral readout, we analyzed the spontaneous activity and the ultrasonic vocalizations (USVs) within the EE cage weekly, and in the open field test at the end of the experiment. In the cage, REE increased the utilization of materials, physical activity, and the rate of appetitive USVs. In the OF, the CEE-induced enhancements in novelty habituation and social signaling were equaled by the REE. At the neural level, we measured the expression of genes related to neural plasticity and epigenetic regulations in different brain regions. In the dorsal striatum and hippocampus, REE upregulated the expression of the brain-derived neurotrophic factor, its tropomyosin kinase B receptor, and the DNA methyltransferase 3A. Altogether, our results suggest that the higher activity within the cage and the augmented incentive motivation provoked by the REE boosted its neurobehavioral effects equaling or surpassing those observed in the CEE condition. As constant exposures to treatments or stimulating environments are virtually impossible for humans, restricted EE protocols would have greater translational value than traditional ones.

Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery

Hypoxic damage to the developing brain due to preterm birth causes many anatomical changes, including damage to the periventricular white matter. This results in the loss of glial cells, significant disruptions in myelination, and thereby cognitive and behavioral disabilities seen throughout life. Encouragingly, these neurological morbidities can be improved by environmental factors; however, the underlying cellular mechanisms remain unknown. We found that early and continuous environmental enrichment selectively enhances endogenous repair of the developing white matter by promoting oligodendroglial maturation, myelination, and functional recovery after perinatal brain injury. These effects require increased exposure to socialization, physical activity, and cognitive enhancement of surroundings—a complete enriched environment. Using RNA-sequencing, we identified oligodendroglial-specific responses to hypoxic brain injury, and uncovered molecular mechanisms involved in enrichment-induced recovery. Together, these results indicate that myelin plasticity induced by modulation of the neonatal environment can be targeted as a therapeutic strategy for preterm birth.

Continuous environmental enrichment and aerobic exercise improves spatial memory: focus on rat hippocampal BDNF and NGF

Memory is an important cognitive function in humans. Exercise and environmental enrichment (EE) exposure have positive effects on memory function via improved neurogenesis through expression of growth factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Exercise and environmental enrichment have independently been shown to increase BDNF and NGF, but the effect of the combination of these treatments has not been widely studied. This experimental study aims to analyse the effect of aerobic exercise, EE exposure, and combination of aerobic exercise and EE exposure on memory function. This study used twenty 7-month old male Wistar rats that were given treatment for 8 weeks. Memory function was tested using forced alternation Y-maze. Hippocampal expression of BDNF and NGF were also assessed. The results showed the combination group has highest performance in memory function test and also the highest level of hippocampal BDNF and NGF (P&lt;0.05). It can be concluded that the combination of aerobic exercise and continuous EE exposure produces the best results for memory function through higher levels of hippocampal BDNF and NGF in adult rats.

Effect of continuous environmental enrichment and aerobic exercise on rat plasma and hippocampal brain-derived neurotrophic factor

Objective: Environmental enrichment (EE) or exercise can positively affect memory function through increased long-term potentiation and neurogenesis, which is facilitated by brain-derived neurotrophic factor (BDNF). BDNF promotes blood vessel growth, angiogenesis linked to adult neurogenesis, and neuronal survival. Here, we investigated the effects of EE, aerobic exercise, and their combination on plasma and hippocampal BDNF levels. Materials and Methods: Twenty-four 7-month-old adult male Wistar rats weighing 300–400 g were randomly assigned to the following four groups: control (C), aerobic exercise (A), EE, and combined EE and aerobic exercise (EEA). Interventions were given for 8 weeks, and plasma and hippocampal BDNF levels were measured using enzyme-linked immunosorbent assay. Results: A combination of aerobic exercise and continuous EE produced the largest increase in hippocampal and plasma BDNF levels in adult rats. A positive correlation (r = 0.686, P = 0.002, n = 24) was observed between plasma and hippocampal BDNF levels in adult rats. Conclusion: We conclude that a combination of aerobic exercise and continuous EE increases plasma and hippocampal BDNF in adult rats.

Combination of Aerobic Exercise and Continuous Environmental Enrichment Improves Adult Male Rats’ Spatial Memory: Study on Hippocampal Insulin Like Growth Factor 1 (IGF-1) and Fibroblast Growth Factor 2 (FGF-2) Expression

BACKGROUND: Memory declines with the progression of age through the neurodegeneration process. Aerobic exercise and environmental enrichment can delay neurodegeneration by improving neuroplasticity via expression of insulin like growth factor 1 (IGF-1), fibroblast growth factor 2 (FGF-2) and other proteins. Combination treatment of aerobic exercise and continuous environmental enrichment and their effect on the expression of IGF-1 and FGF-2 which were expected to improve memory function has not been studied previously. Thus, this study aimed to observe it.METHODS: This is an experimental research using 24 male Wistar rats (Rattus norvegicus, 300-400 g, age 7-8 months) divided randomly into 4 groups: control (C), aerobic exercise (A), continuous (EE), and combination of aerobic exercise and continuous environmental enrichment (A-EE). At the end of an 8-week treatment, rats were sacrificed, and an enzyme-linked immunosorbent assay (ELISA) examination was performed to assess hippocampal IGF-1 and FGF-2 levels.RESULTS: In the 8th week, A-EE group showed the best improvement in rats’ spatial memory (47.84±10.6 %) followed by EE group (45.03±4.1 %), A group (38.61±3.8 %), and C group (22.76±7.12 %). However, A-EE group’s hippocampal IGF-1 (16.21±7.56 ng/mg protein) and FGF-2 (1.29±0.57 ng/mg protein) expression were not higher than other groups.CONCLUSION: Improvement in memory function in the combination group is a result of induction of various growth factors’ expression in the hippocampus, including IGF-1 and FGF-2, but the primary pathway of memory function improvement may be from other growth factors.KEYWORDS: spatial memory, aerobic exercise, environmental enrichment, hippocampus, IGF-1, FGF-2

Delayed and Abbreviated Environmental Enrichment after Brain Trauma Promotes Motor and Cognitive Recovery That Is Not Contingent on Increased Neurogenesis.

Environmental enrichment (EE) confers motor and cognitive recovery in pre-clinical models of traumatic brain injury (TBI), and neurogenesis has been attributed to mediating the benefits. Whether that ascription is correct has not been fully investigated. Hence, the goal of the current study is to further clarify the possible role of learning-induced hippocampal neurogenesis on functional recovery after cortical impact or sham injury by utilizing two EE paradigms (i.e., early + continuous, initiated immediately after TBI and presented 24 h/day; and delayed + abbreviated, initiated 4 days after TBI for 6 h/day) and comparing them to one another as well as to standard (STD) housed controls. Motor and cognitive performance was assessed on post-operative Days 1-5 and 14-19, respectively, for the STD and early + continuous EE groups and on Days 4-8 and 17-22, for the delayed + abbreviated EE groups. Rats were injected with bromodeoxyuridine (BrdU, 500 mg/ kg; intraperitoneally) for 3 days (12 h apart) before cognitive training and sacrificed 1 week later for quantification of BrdU+ and doublecortin (DCX+) labeled cells. Both early + continuous and delayed + abbreviated EE promoted motor and cognitive recovery after TBI, relative to STD (p < 0.05), and did not differ from one another (p > 0.05). However, only early + continuous EE increased DCX+ cells beyond the level of STD-housed controls (p < 0.05). No effect of EE on non-injured controls was observed. Based on these data, two novel conclusions emerged. First, EE does not need to be provided early and continuously after TBI to confer benefits, which lends credence to the delayed + abbreviated EE paradigm as a relevant pre-clinical model of neurorehabilitation. Second, the functional recovery observed after TBI in the delayed + abbreviated EE paradigm is not contingent on increased hippocampal neurogenesis. Future studies will elucidate alternate viable mechanisms mediating the benefits induced by EE.

Refining environmental enrichment to advance rehabilitation based research after experimental traumatic brain injury

The typical environmental enrichment (EE) paradigm, which consists of continuous exposure after experimental traumatic brain injury (TBI), promotes behavioral and histological benefits. However, rehabilitation is often abbreviated in the clinic and administered in multiple daily sessions. While recent studies have demonstrated that a once daily 6-hr bout of EE confers benefits comparable to continuous EE, breaking the therapy into two shorter sessions may increase novelty and ultimately enhance recovery. Hence, the aim of the study was to test the hypothesis that functional and histological outcomes will be significantly improved by daily preclinical neurorehabilitation consisting of two 3-hr periods of EE vs. a single 6-hr session. Anesthetized adult male rats received a controlled cortical impact of moderate-to-severe injury (2.8mm tissue deformation at 4m/s) or sham surgery and were then randomly assigned to groups receiving standard (STD) housing, a single 6-hr session of EE, or two 3-hr sessions of EE daily for 3weeks. Motor function (beam-balance/traversal) and acquisition of spatial learning/memory retention (Morris water maze) were assessed on post-operative days 1–5 and 14–19, respectively. Cortical lesion volume was quantified on day 21. Both EE conditions improved motor function and acquisition of spatial learning, and reduced cortical lesion volume relative to STD housing (p<0.05), but did not differ from one another in any endpoint (p>0.05). The findings replicate previous work showing that 6-hr of EE daily is sufficient to confer behavioral and histological benefits after TBI and extend the findings by demonstrating that the benefits are comparable regardless of how the 6-hrs of EE are accrued. The relevance of the finding is that it can be extrapolated to the clinic and may benefit patients who cannot endure a single extended period of neurorehabilitation.

Differential effects of intermittent and continuous exposure to novel environmental stimuli on the development of amphetamine-induced behavioral sensitization in mice: Implications for addiction

BackgroundPrevious studies have demonstrated a preventive effect of continuous environmental enrichment during early development on the vulnerability of rodents to drug addiction-related behaviors. Recently, it was demonstrated that a continuous environmental enrichment could eliminate already established addiction-related behaviors in mice. The present study compared the effects of intermittent or continuous exposure to novel stimuli during repeated amphetamine (Amp) treatment on the development of behavioral sensitization (an animal model of addiction-related neuroadaptations) in adult mice. MethodsThree-month-old male Swiss mice were treated with 2.5mg/kg Amp every other day for 13 days in their home cages. Novel objects were presented in their home cages for 2h on non-drug treatment days (experiment 1) or for 24h/day during the 13 days of drug treatment (experiment 2). Seven days after the drug treatment had finished, the mice were challenged with 2.5mg/kg Amp, and their locomotor activity was quantified in a familiar open field for 10min. ResultsIntermittent exposure to the novel objects did not modify the acute Amp locomotor stimulatory effect but potentiated the development of Amp-induced locomotor sensitization. This enhanced sensitization was due to increased locomotion in the central squares of the apparatus, which suggests anxiolysis or increased impulsiveness. Conversely, continuous exposure to the novel objects potentiated the acute Amp locomotor stimulatory effect and blunted the development of Amp-induced locomotor sensitization. ConclusionsWe conclude that addiction-related behaviors can be differentially and critically modified depending on the schedule and period of the novelty exposure.

Continuous enriched environment improves learning and memory in adult NMRI mice through theta burst-related-LTP independent mechanisms but is not efficient in advanced aged animals

IntroductionEffects of 3-month continuous environmental enrichment (EE) on cognitive abilities and on theta burst-related synaptic plasticity of CA1 hippocampal neuronal networks have been assessed in 6- and 20-month old NMRI female mice. ResultsEE decreased anxiety-like behavior and improved learning and memory performances in adult but not in aged mice. Electrophysiological results in CA1 hippocampal slices showed that basal synaptic transmission was not affected by EE in adult mice whereas it was partially improved in aged animals, even though not sufficient to rescue the decrease related to aging. Besides, no effect of EE on N-methyl-d-aspartate receptor activation and theta-burst-induced long-term potentiation was found in adult or aged animals. DiscussionThese results indicate that continuous EE is able to improve cognitive abilities in adult NMRI female mice, that does not correlate with changes in theta burst-related synaptic plasticity within neuronal networks. In addition, the lack of effects in aged animals suggests the existence of a critical delay for the beneficial effects of EE on cognitive aging.

Abbreviated Environmental Enrichment Enhances Neurobehavioral Recovery Comparably to Continuous Exposure After Traumatic Brain Injury

Background. Environmental enrichment (EE) is a complex living milieu that has been shown to enhance functional recovery versus standard (STD) housing after experimental traumatic brain injury (TBI) and therefore may be considered a rodent correlate of rehabilitation. However, the typical EE paradigm consists of continuous exposure to enrichment after TBI, which is inconsistent with the limited time frame in clinical rehabilitation. Objective. To determine whether abbreviated EE (ie, rehabilitation-relevant dose response) confers benefits similar to typical EE after TBI. Methods. Adult male rats received either a controlled cortical impact (2.8 mm depth at 4 m/s) or sham injury and were then randomly assigned to TBI + EE, TBI + EE (2 hours), TBI + EE (4 hours), TBI + EE (6 hours), TBI + STD, and respective sham controls. Motor (beam balance/beam walk) and cognitive (Morris water maze) performance was assessed on postoperative days 1 to 5 and 14 to 19, respectively. Results. The TBI + EE (2 hours) and TBI + EE (4 hours) groups were not statistically different from the TBI + STD group in any behavioral assessment. In contrast, the TBI + EE (6 hours) group exhibited significant enhancement of motor and cognitive performance when compared with the TBI + STD group, as well as the TBI + EE (2 hours) and TBI + EE (4 hours) groups (P < .003), and did not differ from the TBI + EE (typical) group. Conclusions. These data demonstrate that abbreviated EE (6 hours) produces motor and cognitive benefits similar to continuous EE after TBI and thus may be considered a dose-relevant rehabilitation paradigm.

P1-068: Environmental enrichment “sessions” are sufficient to provide cognitive benefit to impaired Alzheimer's transgenic mice without affecting brain or plasma Aβ levels

Environmental enrichment (EE) studies using AD mouse models have involved either EE sessions or continuous EE housing. These two EE paradigms, employed separately by different laboratories, are a potential variable that may explain some of the divergent results thus far reported with EE in AD mouse models. Moreover, only our initial study (Neuroreport 15:1751, 2004) investigated the potential of EE to cognitively benefit aged, impaired APPsw transgenic (Tg) mice, with that study showing that continuous EE improves cognitive performance in aged Tg mice. If, however, cognitive stimulation/rehabilitation is to be utilized therapeutically in AD patients, cognitive stimulation “sessions”, given several times weekly, would be the most likely paradigm. Beginning at 10 months of age, APPsw mice were placed in one of four different complex environments (on a rotating basis) for one hour sessions, three times weekly for two months. Additional APPsw mice were placed in continuous EE housing or maintained in standard individual cages for the two month period. A comprehensive behavioral test battery was then administered. Tg mice given EE sessions or continuous EE exhibited similarly-enhanced cognitive performance versus Tg controls in a variety of tasks testing various cognitive domains (e.g., the circular platform task of spatial learning/memory, the platform recognition task of switching from a spatial to a recognition strategy). In the radial arm water maze task of working memory, Tg mice given continuous EE and those given EE sessions also benefited similarly in performing much better than Tg controls and identical to non-transgenic controls. Evaluation of plasma and hippocampal Aβ1–40 and Aβ1–42 (both soluble and insoluble) revealed no effects of either EE sessions or continuous EE in Tg mice versus Tg controls. Thus, EE “sessions” provided cognitive benefits in aged APPsw mice that were similar to those resulting from continuous EE, with neither paradigm impacting Aβ levels. We conclude that EE sessions are sufficient to provide cognitive benefit to aged Tg mice through Aβ independent mechanisms, suggesting that frequent and long-term cognition stimulation/rehabilitation sessions could be of substantial cognitive benefit to AD patients irrespective of their brain Aβ burdens.

Early enriched housing results in partial recovery of memory deficits in female, but not in male, rats after neonatal hypoxia–ischemia

Our previous results indicated that stimulation by daily environmental enrichment (EE) recovered memory deficits without affecting hippocampus damage in adult male rats submitted to neonatal hypoxia–ischemia (HI). The present study investigated whether early continuous housing in an enriched environment would be effective in preventing spatial and recognition memory both in adolescent and adult female and male rats, as well as the possible benefits of continuous EE in alleviating hippocampal and striatal atrophy consequent to the neonatal HI. Wistar rats in the 7th PND were submitted to the HI and, in the day after, were housed in an enriched environment (8th–30th PND). Subsequently, performance of animals in the novel-object recognition and in two water maze tasks was assessed; in adulthood, animals' behavior was reassessed in the water maze. Rats were sacrificed and both hippocampal volume and striatal area were estimated following the completion of behavioral study. Post-HI cognitive deficits in the object recognition test were completely recovered by the EE. However, memory impairment in the water maze was only partially prevented by EE; this effect was observed especially in female rats on the working memory protocol. As for the morphological assessment, there was no enrichment effect over the loss of hippocampus volume and striatum area. In conclusion, present data indicate that early housing in EE caused performance recovery in object recognition and a partial improvement in the working memory spatial task in adolescent females after neonatal HI; however no effects of enrichment were revealed in adult animal's performance or in the extension of tissue atrophy of hippocampus and striatum consequent to HI.

Environmental enrichment-mediated functional improvement after experimental traumatic brain injury is contingent on task-specific neurobehavioral experience

Environmental enrichment (EE) is superior to standard (STD) housing in promoting functional recovery after traumatic brain injury (TBI). However, whether the EE-mediated benefits after TBI are dependent on exposure to enrichment during neurobehavioral training has not been elucidated. To address this issue, isoflurane-anesthetized adult male rats received either a cortical impact or sham injury and were then randomly assigned to early EE, delayed EE, continuous EE or no EE (i.e., STD conditions). Continuous EE or no EE was initiated immediately after surgery and continued for the duration of the study. Early EE began directly after surgery, continued for 1 week, and was then followed by STD living (2 rats per cage) for the remainder of the study, while delayed EE commenced 1 week after early STD housing. Functional outcome was assessed with established motor and cognitive tests on post-injury days 1–5 and 14–18, respectively. CA1/CA3 neurons were quantified at 3 weeks. CA3 cell loss was significantly attenuated in the TBI+continuous EE group versus the TBI+no EE group. Beam-walking was facilitated in the TBI groups that received either early or continuous EE versus those receiving delayed or no EE. Cognitive training was enhanced in the TBI groups that received continuous or delayed EE versus the early EE or no EE groups. These data suggest that EE-mediated functional improvement after TBI is contingent on task-specific neurobehavioral experience.