Enriched Environment Exposure Research Articles

Maternal exposure to an enriched environment promotes uterine vascular remodeling and prevents embryo loss in mice.

Implantation-related events are crucial for pregnancy success. In particular, defects in vascular remodeling at the maternal-fetal interface are associated with spontaneous miscarriage and recurrent pregnancy loss. Physical activity and therapies oriented to reduce stress improve pregnancy outcomes. In animal models, environmental stimulation and enrichment are associated with enhanced well-being, cognitive function and stress resilience. Here, we studied whether the exposure of BALB/c mice to an enriched environment (EE) regulates crucial events during early gestation at the maternal-fetal interface. Pregnant BALB/c mice were exposed to the EE that combines non-invasive stimuli from the sensory pathway with voluntary physical activity. The pregnancy rate was evaluated. Implantation sites were investigated microscopically and macroscopically. Vascular adaptation parameters at the maternal-fetal interface were analyzed. We found that exposure to the EE prevented pregnancy loss between gestational days 7 and 15. Also, it increased the diameter of the uterine artery and decreased the wall:lumen ratio of the mesometrial decidual vessels, suggesting that EE exposure promotes vascular remodeling. Moreover, it increased nitric oxide synthase activity and inducible nitric oxide synthase expression, as well as prostaglandin F2a production and endoglin expression in the implantation sites. Exposure of pregnant females to the EE regulates uterine physiology, promoting vascular remodeling during early gestation. These adaptations might contribute to preventing embryo loss. Our results highlight the importance of the maternal environment for pregnancy success. The design of an 'EE-like' protocol for humans could be considered as a new non-pharmacologic strategy to prevent implantation failure and recurrent miscarriage.

Effect of environmental enrichment on behavioral and morphological outcomes following neonatal hypoxia-ischemia in rodent models: A systematic review and meta-analysis

Neonatal hypoxia-ischemia (HI) is a major cause of mortality and morbidity in newborns and, despite recent advances in neonatal intensive care, there is no definitive treatment for this pathology. Once preclinical studies have shown that environmental enrichment (EE) seems to be a promising therapy for children with HI, the present study conducts a systematic review and meta-analysis of articles with EE in HI rodent models focusing on neurodevelopmental reflexes, motor and cognitive function as well as brain damage. The protocol was registered a priori at PROSPERO. The search was conducted in PubMed, Embase and PsycINFO databases, resulting in the inclusion of 22 articles. Interestingly, EE showed a beneficial impact on neurodevelopmental reflexes (SMD= -0.73, CI= [-0.98; -0.47], p< 0.001, I2= 0.0%), motor function (SMD= -0.55, CI= [-0.81; -0.28], p< 0.001, I2= 62.6%), cognitive function (SMD= -0.93, CI= [-1.14; -0.72], p< 0.001, I2= 27.8%) and brain damage (SMD= -0.80, CI= [-1.03; -0.58], p< 0.001, I2= 10.7%). The main factors that potentiate EE positive effects were enhanced study quality, earlier age at injury as well as earlier start and longer duration of EE exposure. Overall, EE was able to counteract the behavioral and histological damage induced by the lesion, being a promising therapeutic strategy for HI.

Environmental Enrichment Facilitates Anxiety in Conflict-Based Tests but Inhibits Predator Threat-Induced Defensive Behaviour in Male Mice

Introduction: Environmental enrichment (EE) is a useful and sophisticated tool that improves rodents’ well-being by stimulating social behaviour and cognitive, motor, and sensory functions. Exposure to EE induces neuroplasticity in different brain areas, including the limbic system, which has been implicated in the control of anxiety and fear. However, the effects of EE on ethologically relevant naturalistic behaviours, such as those displayed by prey in the presence of predators, remain largely unexplored. Material and Methods: In the present study, we investigated anxiety- and panic attack-like behaviours in a predator (cat)-prey confrontation paradigm and compared them with those in classical assays, such as the elevated plus-maze (EPM), marble-burying, and open field tests (OFTs), using C57BL/6J male mice housed in enriched or standard environments for 6 weeks. Results: We observed that EE exposure caused enhancement of the levels of anxiety-like behaviours in the EPM and OFTs, increasing risk assessment (an anxiety-related response), and decreasing escape (a panic attack-like response) behaviours during exposure to the predator versus prey confrontation paradigm. Conclusion: Taken together, our findings suggest that enriched external environments can modify the processing of fear- and anxiety-related stimuli in dangerous situations, changing the decision-making defensive strategy.

Adolescent enriched environment exposure alleviates cognitive impairments in sleep-deprived male rats: Role of hippocampal brain-derived neurotrophic factor.

Developmental life experience has long-lasting influences on the brain and behavior. The present study aims to examine the long-term effects of the enriched environment (EE), which was imposed during the adolescence period of life, on their passive avoidance and recognition memories as well as anxiety-like behaviors and hippocampal brain-derived neurotrophic factor (BDNF) levels, in sleep-deprived male rats. In the present study, the male pups were separated from their mothers in postnatal day 21 (PND21) and were housed in the standard or EE for 40 days. In PND 61, the rats were allocated in four groups: control, SD (sleep deprivation), EE, and EE + SD groups. SD was induced in rats by a modified multiple platform model for 24 h. Open field, novel object recognition memory, and passive avoidance memory tests were used to examine behavior and cognitive ability. The expression of hippocampal BDNF levels was determined by PCR. The results revealed that SD increased anxiety-like behaviors and impaired cognitive ability, while adolescent EE housing alleviated these changes. In addition, EE reversed SD-induced changes in hippocampal BDNF level. We also demonstrated that EE not only has beneficial effects on the cognitive functions of normal rats but also declined memory deficits induced by SD. In conclusion, our results suggest that housing in EE during the adolescence period of life reduces cognitive impairment induced by SD. The increase of the BDNF level in the hippocampus is a possible mechanism to alleviate cognitive performance in sleep-deprived rats.

A novel viewpoint in glaucoma therapeutics: enriched environment.

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

Enriched environment and visual stimuli protect the retinal pigment epithelium and photoreceptors in a mouse model of non-exudative age-related macular degeneration

Non-exudative age-related macular degeneration (NE-AMD), the main cause of blindness in people above 50 years old, lacks effective treatments at the moment. We have developed a new NE-AMD model through unilateral superior cervical ganglionectomy (SCGx), which elicits the disease main features in C57Bl/6J mice. The involvement of oxidative stress in the damage induced by NE-AMD to the retinal pigment epithelium (RPE) and outer retina has been strongly supported by evidence. We analysed the effect of enriched environment (EE) and visual stimulation (VS) in the RPE/outer retina damage within experimental NE-AMD. Exposure to EE starting 48 h post-SCGx, which had no effect on the choriocapillaris ubiquitous thickness increase, protected visual functions, prevented the thickness increase of the Bruch’s membrane, and the loss of the melanin of the RPE, number of melanosomes, and retinoid isomerohydrolase (RPE65) immunoreactivity, as well as the ultrastructural damage of the RPE and photoreceptors, exclusively circumscribed to the central temporal (but not nasal) region, induced by experimental NE-AMD. EE also prevented the increase in outer retina/RPE oxidative stress markers and decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, EE increased RPE and retinal brain-derived neurotrophic factor (BDNF) levels, particularly in Müller cells. When EE exposure was delayed (dEE), starting at 4 weeks post-SCGx, it restored visual functions, reversed the RPE melanin content and RPE65-immunoreactivity decrease. Exposing animals to VS protected visual functions and prevented the decrease in RPE melanin content and RPE65 immunoreactivity. These findings suggest that EE housing and VS could become an NE-AMD promising therapeutic strategy.

Enriched Environment Modulates Sharp Wave-Ripple (SPW-R) Activity in Hippocampal Slices.

Behavioral flexibility depends on neuronal plasticity which forms and adapts the central nervous system in an experience-dependent manner. Thus, plasticity depends on interactions between the organism and its environment. A key experimental paradigm for studying this concept is the exposure of rodents to an enriched environment (EE), followed by studying differences to control animals kept under standard conditions (SC). While multiple changes induced by EE have been found at the cellular-molecular and cognitive-behavioral levels, little is known about EE-dependent alterations at the intermediate level of network activity. We, therefore, studied spontaneous network activity in hippocampal slices from mice which had previously experienced EE for 10–15 days. Compared to control animals from standard conditions (SC) and mice with enhanced motor activity (MC) we found several differences in sharp wave-ripple complexes (SPW-R), a memory-related activity pattern. Sharp wave amplitude, unit firing during sharp waves, and the number of superimposed ripple cycles were increased in tissue from the EE group. On the other hand, spiking precision with respect to the ripple oscillations was reduced. Recordings from single pyramidal cells revealed a reduction in synaptic inhibition during SPW-R together with a reduced inhibition-excitation ratio. The number of inhibitory neurons, including parvalbumin-positive interneurons, was unchanged. Altered activation or efficacy of synaptic inhibition may thus underlie changes in memory-related network activity patterns which, in turn, may be important for the cognitive-behavioral effects of EE exposure.

Modulating adult neurogenesis affects synaptic plasticity and cognitive functions in mouse models of Alzheimer's disease.

SummaryNew neurons are abnormal in the adult hippocampus of Alzheimer's disease (AD) mouse models. The effects of modulating adult neurogenesis on AD pathogenesis differ from study to study. We reported recently that ablation of adult neural stem cells (aNSCs) was associated with improved memory in AD models. Here, we found that long-term potentiation (LTP) was improved in the hippocampus of APP/PS1 mice after ablation of aNSCs. This effect was confirmed in hAPP-J20 mice, a second AD mouse model. On the other hand, we found that exposure to enriched environment (EE) dramatically increased the number of DCX+ neurons, promoted dendritic growth, and affected the location of newborn neurons in the dentate gyrus of APP/PS1 mice, and EE exposure significantly ameliorated memory deficits in APP/PS1 mice. Together, our data suggest that both inhibiting abnormal adult neurogenesis and enhancing healthy adult neurogenesis could be beneficial for AD, and they are not mutually exclusive.

Environmental enrichment modulates silent information regulator 1 (SIRT1) activity to attenuate central presbycusis in a rat model of normal aging.

Age-related hearing loss (ARHL) is sensory impairment in the elderly. This study aimed to identify a critical molecular mechanism that can maintain young phenotypes. We focused on the effect of exposure to environmental enrichment (EE) for 12weeks in the central auditory pathway and limbic system of aged rats. The effects of EE were compared with the effects of dexamethasone administration. We found that in 74-week-old rats hearing function was significantly reduced and the number of neuronal specific nuclear protein (NeuN)-positive cells was decreased by 10-15% in the auditory cortex, amygdala, and hippocampus. EE exposure did not significantly affect the number of neurons, but DX administration significantly decreased their numbers in the amygdala compared with untreated aged rats. Both treatments reduced inducible nitric oxide synthase (iNOS) expression in the auditory pathway and limbic system. Exposure to EE significantly increased silent information regulator 1 (SIRT1) expression and activity, and nicotinamide phosphoribosyltransferase (NAMPT) concentration. In this study, the exposure to EE resulted in attenuated age-related hearing loss accompanied by reduction of iNOS expression and increase SIRT1 activity and NAMPT level. These data showed that EE may be a potential therapeutic to prevent ARHL.

Environmental Enrichment Induces Meningeal Niche Remodeling through TrkB-Mediated Signaling.

Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli, including environmental enrichment (EE) acting through BDNF-TrkB signaling. We have recently identified NPs in meninges; however, the meningeal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of EE exposure on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of the meningeal cell number and proliferation, we observed an increased number of neural precursors in the meninges. A lineage tracing experiment suggested that EE-induced β3-Tubulin+ immature neuronal cells present in the meninges originated, at least in part, from GLAST+ radial glia cells. To investigate the molecular mechanism responsible for meningeal reaction to EE exposure, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced meningeal niche changes. Overall, these data showed, for the first time, that EE exposure induced meningeal niche remodeling through TrkB-mediated signaling. Fluoxetine treatment further confirmed the meningeal niche response, suggesting it may also respond to other pharmacological neurogenic stimuli. A better understanding of the neurogenic stimuli modulation for meninges may be useful to improve the effectiveness of neurodegenerative and neuropsychiatric treatments.

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence-accelerated mouse prone 8 mice.

A previous study demonstrated that middle-aged (5-6 months of age) senescence-accelerated mouse prone 8 (SAMP8) mice can be used as animal models of mild cognitive impairment (MCI). An enriched environment (EE) can mitigate cognitive decline and decrease the pathological changes associated with various neurodegenerative diseases. In the present study, the learning-memory abilities of SAMP8 mice during the MCI phase (5 months of age) was evaluated and neuropathological changes in the hippocampus were examined after the mice were exposed to an EE for 60 days. In the Morris water maze test, EE-exposed mice demonstrated significantly decreased escape latency and increased time spent in the target quadrant and number of platform crossings compared with control mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining showed that EE-exposed mice had reduced neuronal apoptosis and increased number of surviving neurons compared with control mice. Golgi staining, transmission electron microscopy, and immunohistochemical staining demonstrated that EE-exposed mice exhibited increased dendritic spine densities among secondary and tertiary apical dendrites; increases in synaptic numerical density, synaptic surface density, and expression of synaptophysin; and reduced deposition of amyloid-β (Aβ) and expression of amyloid-precursor protein (APP) in the hippocampal CA1 region compared with control mice. These results demonstrate that EE exposure effectively decreases neuronal loss and regulates neuronal synaptic plasticity by reducing the expression of APP and the deposition of Aβ in the hippocampal CA1 region, thereby mitigating cognitive decline in SAMP8 mice during the MCI phase and delaying the progression from MCI to Alzheimer's disease.

Brief Environmental Enrichment exposure enhances contextual-induced sucrose-seeking with and without memory reactivation in rats

Chronic Environmental Enrichment (EE) has been shown to prevent the relapse to addictive behaviours, such as drug-taking and -seeking. Recently, acute EE was shown to reduce cue-induced sucrose-seeking, but its effects on contextual (Cx)-induced sucrose-seeking is still unknown. Here we report the effects of brief EE exposure on Cx-induced sucrose-seeking with and without prior Cx-memory reactivation.Adult male Sprague-Dawley rats were trained to sucrose self-administration associated to a specific conditioning Cx (CxA), followed by a 7-day extinction in a different Cx (CxB). Afterwards, rats were exposed for 22 h to EE, and 1 h later to either i) Cx-induced sucrose-seeking (1 h, renewal without Cx-memory reactivation), ii) or two different Cx-memory reactivations: short (2-min) and long (15-min) CxA-retrieval session (Cx-Ret). In Cx-Ret experiments, CxA-induced sucrose-seeking test (1 h) was done after a subsequent 3-day extinction phase. The assessment of molecular markers of memory reactivation/reconsolidation, Zif-268 and rpS6P, was performed 2 h after Cx-Ret.Brief EE exposure enhanced Cx-induced sucrose-seeking without and with short but not long Cx-retrieval. Moreover, EE impaired discriminative responding at test prior to long, whereas improved it with or without short Cx-retrieval. Different changes in Zif-268 and rpS6P expression induced by short vs. long Cx-Ret were correlated to behavioural data, suggesting the occurrence of different memory processes affected by EE.Our data show that brief EE exposure may differently affect subsequent appetitive relapse depending on the modality of re-exposure to conditioned context. This finding suggests caution and further studies to understand the proper conditions for the use of EE against appetitive and addiction disorders.

Efficacy of choline and DHA supplements or enriched environment exposure during early adult obesity in mitigating its adverse impact through aging in rats.

IntroductionThe aim of this study was to assess the efficacy of choline and DHA or exposure to environmental enrichment in obese adult and aging rats on alterations in body mass index, serum lipid profile and arterial wall changes, despite stopping high fat diet consumption and interventions during adulthood.Methods21 day old male Sprague Dawley rats were assigned as Experiment-1 & 2 - PND rats were divided into 4 groups with interventions for 7 months (n = 8/group). NC– Normal control fed normal chow diet; OB- Obese group, fed high fat diet; OB + CHO + DHA- fed high fat diet and oral supplementation of choline, DHA. OB + EE- fed high fat diet along with exposure to enriched environment .Experiment-2 had similar groups and interventions as experiment 1 but for next 5 months were fed normal chow diet without any interventions. Body mass index was assessed and blood was analyzed for serum lipid profile. Common Carotid Artery (CCA) was processed for Haematoxylin and eosin, Verhoff Vangeison stains. Images of tissue sections were analyzed and quantified using image J and tissue quant software.ResultsIn experiment.1, mean body mass index (p < 0.001), serum lipid profile (p < 0.01), thickness of tunica intima (p < 0.05), tunica media (p < 0.01) and percentage of collagen fibers (p < 0.01) of CCA were significantly increased in OB compared to NC. These were significantly attenuated in OB + CHO + DHA and OB + EE compared to OB. In experiment.2, mean body mass index (p < 0.01), serum lipid profile (p < 0.05) and thickness of tunica media of CCA (p < 0.01) were significantly increased in OB compared to NC. In OB + CHO + DHA and OB + EE, significant attenuation was observed in mean body mass index and mean thickness of tunica media compared to same in OB.ConclusionAdult obesity has negative impact on body mass index, serum lipid profile and arterial wall structure that persists through aging. Supplementation of choline and DHA or exposure to enriched environment during obesity attenuates these negative impacts through aging.

Coconut oil supplementation during development reduces brain excitability in adult rats nourished and overnourished in lactation.

Coconut oil has been considered as a therapeutic alternative in several pathologies, but there is limited information regarding its effects on brain functioning. This study analyzed whether early virgin coconut oil (VCO) supplementation interferes with electrical activity of the adult rat brain and its lipid peroxidation. Moreover, it investigated whether the putative effect on brain electrophysiology could be affected by overnutrition occurring during lactation, and/or by environmental enrichment (EE). Electrophysiology was measured through cortical spreading depression (CSD), a phenomenon related to brain excitability. Wistar rats were suckled in litters of either nine or three pups, forming nourished (N) or overnourished (ON) groups, respectively. Between the 7th and 30th days of life, half of the animals in each group received VCO (10 mg kg-1 d-1; by gavage). The other half received an equivalent amount of vehicle (V, 0.009% cremophor). On day 36, animals from both groups were subjected to EE for 4 weeks. At 105 ± 15 days of life, each animal was subjected to CSD recordings and lipid peroxidation analyses. Overnutrition during lactation enhanced body and brain weights. VCO decelerated the CSD propagation velocity (control - 3.57 ± 0.23 mm min-1versus VCO - 3.27 ± 0.18 mm min-1; p < 0.001), regardless of whether subjected to overnourishment or EE exposure. Neither VCO nor EE modified the cerebral lipid peroxidation (p > 0.05). VCO supplementation impaired the spreading of CSD, indicating reduction of brain excitability. VCO effects occurred regardless of the nutritional state during lactation.

Enrichment Environment Positively Influences Depression- and Anxiety-Like Behavior in Serotonin Transporter Knockout Rats through the Modulation of Neuroplasticity, Spine, and GABAergic Markers.

The serotonin transporter (5-HTT in humans, SERT in rodents) is the main regulator of serotonergic transmission in the brain. The short allelic variant of the 5-HTT gene is in humans associated with psychopathologies and may enhance the vulnerability to develop depression after exposure to stressful events. Interestingly, the short allele also increases the sensitivity to a positive environment, which may buffer the vulnerability to depression. Since this polymorphism does not exist in rodents, male SERT knockout (SERT−/−) rats were tested to explore the molecular mechanisms based on this increased predisposition. This article investigates the influences of a positive manipulation, namely, enriched environment (EE), on the depressive-like behavior observed in SERT−/− rats. We found that one month of EE exposure normalized the anhedonic and anxious-like phenotype characteristics of this animal model. Moreover, we observed that EE exposure also restored the molecular alterations in the prefrontal cortex by positively modulating the expression of the neurotrophin Bdnf, and of spines and gamma-aminobutyric acid (GABA)ergic markers. Overall, our data confirm the depression-like phenotype of SERT−/− rats and highlight the ability of EE to restore behavioral and molecular alterations, thus promoting the opportunity to use EE as a supporting non-pharmacological approach to treat mood disorders.

Short-term but not long-term exposure to an enriched environment facilitates the extinction of aversive memory

Environmental enrichment (EE) has been used to investigate behavioral changes and neuroplasticity in brain in normal and pathological conditions. Besides, the EE has been used to understand the neurobehavioral systems involved in learning experiences, visual inputs, defensive responses, social interactions and memory. However, the required exposure duration to remove aversive memories remains lacking. Therefore, the purpose of the present study was to investigate the time-course effect of EE exposure on the extinction of aversive memory. Young adult male Wistar rats were exposed to two different EE protocols: short-term environmental enrichment (EE2 – animal kept under enriched conditions for two weeks) and long-term environmental enrichment (EE4 – animal kept under enriched conditions for four weeks). The contextual fear conditioning test was used to assess aversive memory. The both EE protocols provide changes in Zif-268 immunoreactivity in mesocorticolimbic areas such as CA1 and central amygdala; however, only short-term EE reduces the ZIF-268 immunoreactivity in VTA. Besides, both EE protocols also provide an increase in TH immunoreactivity in VTA and nucleus accumbens, but only the short-term EE modifies the TH immunoreactivity in CA1 and infralimbic region of the prefrontal cortex. The time-course effect of EE interferes differently on the extinction of aversive memory, being two weeks of exposure with EE sufficient to cause improvement in coping during aversive situations, favoring the extinction of conditioned fear memory.

HDAC2 (Histone deacetylase 2): A critical factor in environmental enrichment-mediated stroke recovery.

Environmental enrichment (EE) is a generally accepted strategy to promote stroke recovery and its beneficial effect is positively correlated with neuroplasticity. However, the mechanisms underlying it remain elusive. Histone deacetylase 2 (HDAC2), a negative regulator of neuroplasticity, is up-regulated after stroke. Thus, we hypothesized that HDAC2 may participate in EE-mediated stroke recovery. In this study, focal stroke was induced by photothrombosis in male mice exposing to EE or standard housing (SH) conditions. Recombinant virus vectors, including Ad-HDAC2-Flag, AAV-CAG-EGFP-Cre, LV-shHDAC2, or their controls were microinjected into the motor cortex at 3days before stroke. Grid-walking and cylinder tasks were conducted to assess motor function. Western blot and immunostaining were used to uncover the mechanisms underlying EE-mediated stroke recovery. We found that EE exposure reversed stroke-induced HDAC2 up-regulation, implicating HDAC2 in EE-mediated functional recovery. Importantly, EE-dependent stroke recovery was counteracted by over-expressing HDAC2, and HDAC2 knockdown promoted functional recovery from stroke to the similar extent as EE exposure. Moreover, the knockdown of HDAC2 epigenetically enhanced expressions of neurotrophins and neuroplasticity-related proteins, with similar effects as EE, and consequently, whole brain and corticospinal tract (CST) rewiring. Together, our findings indicate that HDAC2 is critical for EE-dependent functional restoration. Precisely targeting HDAC2 may mimic EE and serve as a novel therapeutic strategy for stroke recovery.

Effects of exposure to enriched environment during adolescence on passive avoidance memory, nociception, and prefrontal BDNF level in adult male and female rats

Previous studies demonstrated that an enriched environment (EE) exposure improves cognitive functions, synaptic plasticity, neurogenesis, and induction of brain-derived neurotrophic factor (BDNF) in multiple brain regions of laboratory animal models. Also, studies on the sex-dependent effects of exposure to EE during adolescence on adult cognitive functions are less. Therefore, the present experiment was aimed to assess the effects of EE during adolescence on passive avoidance learning and memory, nociception, and prefrontal cortex (PFC) BDNF mRNA levels in the adult male and female rats. Our results indicated that housing in the EE during adolescence improves passive avoidance memory and increases nociceptive response against thermal stimulus in both sexes. Findings of our study also showed an increased BDNF level in the PFC of female animals. As a result, sex differences can affect the expression of BDNF mRNA in the PFC. Further research concerning the precise mechanisms underlying sex hormone-dependent production of BDNF in PFC is critical.

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.

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.