Role of enriched environment in the model of maternal separation / 中国儿童保健杂志

Early life stress in humans can affect the normal development of individual neural networks, ultimately leading to diseases such as anxiety, depression, and autism in such children. The maternal separation model is commonly used to study the effects of early adverse experiences in human infants. Studies have shown that maternal separation in mice can lead to anxiety, depression, and impairments in spatial learning and memory in young mice during adulthood. However, enriched environmental interventions have been found to ameliorate the negative outcomes of early life stress by exerting a range of beneficial effects. This article provides an overview of the positive effects of enriched environmental interventions on mice in the maternal separation model.

Effect of enriched environment combined with acupuncture at head points on behavior in rats with autism spectrum disorder / 中国康复理论与实践

ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.

Effect of enriched environment theory-based multisensory feedback gait training on walking function in stroke patients / 中国康复理论与实践

ObjectiveTo explore the effect of multi-sensory artificial intelligence feedback gait training on the recovery of walking function in stroke patients based on enriched environment theory. MethodsFrom July, 2021 to June, 2023, a total of 80 stroke patients in Huashan Hospital Affiliated to Fudan University were randomly divided into control group (n = 40) and experimental group (n = 40). Both groups received routine rehabilitation in the lying and seated positions, for 40 minutes. The control group received ground walking training, for 20 minutes, while the experimental group received multi-sensory feedback gait training in enriched environment, for 20 minutes. Before and after four weeks intervention, the digital motion monitoring treadmill was used to mearsure step speed, step length, hip and knee swing angle and weight symmetry. They were assessed with Berg Balance scale (BBS), Fugl-Meyer Assessment-Lower Extremities (FMA-LE) and Barthel Index (BI). ResultsAfter intervention, the hip swing angle, step length of both sides and step speed significantly improved in both groups (|t| > 3.162, P < 0.05), and they were better in the experimental group than in the control group (|t| > 2.568, P < 0.05); the average knee joint swing angle and bilateral weight-bearing symmetry significantly improved in the experimental group (|t| > 3.249, P < 0.01); the scores of BBS, FMA-LE and BI improved in both groups (|t| > 3.569, P < 0.01), and they were better in the experimental group than in the control group (|t| > 2.922, P < 0.05). ConclusionMulti-sensory feedback gait training based on enriched environment theory could effectively improve the walking and balance of stroke patients, and increase the ability of independence.

Effects of the enriched environment on pyroptosis in rats with cerebral ischemia-reperfusion injury / 中华老年医学杂志

Objective:To explore the effect of the enriched environment(EE)on pyroptosis in rats with cerebral ischemia-reperfusion injury(CIRI).Methods:45 male Sprague-Dawley rats were randomly divided into three groups: a sham surgery(Sham)group, a cerebral ischemia-reperfusion(CIR)group and an enriched environment(EE)group, with 15 rats in each group.Except for the Sham group, the right middle cerebral artery occlusion model was established in the other two groups.After surgery, the EE group was fed in EE, and the other two groups were fed in standard environment.All the rats were assessed using the modified neurological severity score(mNSS)before modeling and on the 1st day, 7th day and 14th day following surgery.On the 14th day after surgery, 2, 3, 5-triphenyltetrazolium chloride(TTC)staining was used to evaluate the infarct volume, hematoxylin and eosin(HE)staining was used to examine pathomorphological changes of the hippocampal CA1 region on the ischemic side of the rats in each group, immunohistochemical assay was used to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and cysteinyl aspartate specific proteinase-1(caspase-1)proteins in the CA1 region, and ultrastructural changes in neurons in the CA1 region were observed under transmission electron microscopy.Results:Compared with the Sham group, the mNSS scores of the CIR group and the EE group were significantly higher on the 1st day and 7th day after surgery( P<0.05), but there was no significant difference between the CIR and EE groups( P>0.05). On the 14th day after surgery, compared with the CIR group, the EE group showed a decrease in the mNSS score and the cerebral infarct volume( P<0.05), alleviated pathomorphological changes, decreased expression of NLRP3 and caspase-1 proteins( P<0.05), and alleviated pathological changes of pyroptosis in the ultrastructure of neurons. Conclusions:EE can reduce the damage of neurological function, reduce the cerebral infarct volume, and play a protective role for the brain in CIRI rats.The mechanism may be related to the down-regulation of the expression of NLRP3 and caspase-1 proteins related to the classical pyroptosis pathway, leading to the inhibition of pyroptosis.

Effect of augmented reality training based on enriched environment on walking function after stroke / 中国康复理论与实践

ObjectiveTo observe the effect of augmented reality training based on enriched environment on walking dysfunction after stroke. MethodsFrom January, 2021 to June, 2022, 36 stroke patients in the Affiliated Suzhou Hospital of Nanjing University Medical School were randomly divided into control group (n = 18) and experimental group (n = 18). Both groups received conventional rehabilitation treatment. The control group was supplemented with conventional walking training, and the experimental group was supplemented with augmented reality training based on enriched environment, for four weeks. They were assessed with Berg Balance Scale (BBS), Timed Up and Go Test (TUGT), 10-meter walk test (10MWT) and Barthel Index (BI) before and after treatment, and the gait parameter was compared. ResultsNo adverse event occurred during treatment. After treatment, the BBS score, TUGT time, 10MWT speed, BI, gait speed, gait frequency and the proportion of single-leg support on the affected side significantly improved in both groups (|t| > 5.161, P < 0.001). All the above indexes were better in the experimental group than in the control group (|t| > 2.106, P < 0.05), except for BI (t = 1.099, P = 0.282). ConclusionAugmented reality training based on enriched environment could improve the walking function of paitents after stroke, which is better than conventional walking training.

Effects of enriched environment combined with melatonin on learning and memory function and DNA oxidative damage in SAMP8 mice / 中华行为医学与脑科学杂志

Objective:To explore the effects of enriched environment combined with melatonin on learning and memory function and DNA oxidative damage in senescence accelerated mouse prone 8 (SAMP8) mice.Methods:Twenty-four 6-month-old SPF healthy male SAMP8 mice were randomly divided into model group, enriched environment group, melatonin group and enriched environment+ melatonin group, with 6 mice in each group. Six homologous SAMR1 mice of the same age were used as the control group. The mice in the enriched environment group and the enriched environment+ melatonin group were fed in the enriched environment. At the same time, the mice in the melatonin group and the enriched environment+ melatonin group were subcutaneously injected with melatonin (8 mg /(kg·d)) once a day for 28 d. The mice in the model group, the control group and the enriched environment group were subcutaneously injected with an equal volume of 0.9% sodium chloride solution once a day for 28 days. Aging score was used to evaluate the aging of mice. Morris water maze and Y maze tests were used to evaluate the learning and memory ability of mice. The cell morphology of hippocampus in mice was observed by hematoxylin-eosin staining, and the level of Aβ 1-42 protein in hippocampus of mice was detected by immunohistochemical staining. The levels of γ-H2A histone family member X(γ-H2AX) and 8-hydroxy-2 deoxyguanosine(8-OHdG) proteins in hippocampus of mice were detected by Western blot and Enzyme-linked immunosorbent assay. SPSS 25.0 statistical software was used to process the data. One-way analysis of variance was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1)There was a statistical difference in aging scores among the 5 groups of mice after intervention ( F=126.4, P<0.01). After intervention, the aging scores of mice in the enriched environment group, melatonin group, and enriched environment+ melatonin group were lower than that in the model group (all P<0.05), and the score of the enriched environment+ melatonin group was significantly lower than that in the enriched environment group ( P<0.05). (2)The time and group interaction, group main effect and time main effect of the escape latency among the 5 groups of mice were statistically significant ( F=11.2, 799.9, 121.8, all P<0.01). From day 2 to day 4, the escape latencies of mice in the enriched environment group, melatonin group and enriched environment+ melatonin group were significantly lower than that in the model group (all P<0.05). There was a statistically significant difference in the target quadrant residence time and cross-platform times among the 5 groups ( F=70.38, 48.83, both P<0.01). The target quadrant residence time and cross-platform times of mice in the enriched environment group, melatonin group, and enriched environment+ melatonin group were significantly higher than that in the model group (all P<0.05). (3) There were significant differences in the total number of alternations and correct rates among the 5 groups ( F=291.328, 113.482, both P<0.01). The total numbers of alternations and correct rates in melatonin group ((29.46±3.75)times, (53.16±3.47)%) and the enriched environment+ melatonin group((32.57±3.52)times, (58.60±4.13)%)were significantly higher than those in the model group ((18.62±3.96)times, (43.61±3.92) %)(all P<0.05). (4)The results of hematoxylin-eosin staining and immunohistochemistry staining showed that compared with the model group, the cell structure and morphology of the hippocampus of mice in enriched environment group, melatonin group, and enriched environment+ melatonin group were significantly improved, and the expression of Aβ 1-42 was significantly reduced (all P<0.05). (5) There were statistically significant differences in the levels of γ-H2AX and 8-OHdG proteins in the hippocampus of the 5 groups of mice ( F=78.09, 117.20, both P<0.01). The levels of γ-H2AX and 8-OHdG of mice in the enriched environment+ melatonin group ((1.37±0.26), (4.79±0.35)pg/μg) were significantly lower than those in the enriched environment group ((2.83±0.25), (7.23±0.41)pg/μg) and the melatonin group ((2.43±0.22), (6.69±0.28)pg/μg) (all P<0.05). Conclusion:Both enriched environment and melatonin can significantly improve the learning and memory function of SAMP8 mice, and the combined treatment effect is more significant.The mechanism may be related to the reduction of DNA oxidative damage in hippocampus.

Effects of enriched environment on anxiety- and depressive-like behavior and synaptic plasticity in neuropathic pain rats / 中华行为医学与脑科学杂志

Objective:To explore the effect of enriched environment on pain sensitivity, anxiety- and depressive-like behavior in selective nerve injury(SNI) rats model and its potential mechanism.Methods:A total of 36 male clean grade SD rats aged 6-8 weeks were randomly divided into three groups( n=12 in each group): sham operation+ standard environment group (sham group), SNI+ standard environment group (standard environment group), SNI+ enriched environment group (enriched environment group). The rat model of neuropathic pain was established by SNI.The rats in the enriched enviroment group were placed in an enriched enviroment 7 days before operation until 21 days after operation.The paw withdraw threshold(PWT) and paw withdraw latency (PWL) were performed to assess hyperalgesia.The open field test, elevated plus maze test, novelty suppressed feeding test and forced swimming test were used to assess anxiety and depression like behavior.The expressions of cAMP response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95) and neuroligin 2 (NLGN2) were detected by Western blot.The expression of CREB and BDNF in contralateral ACC were measured by immunofluorescence.GraphPad prism 8.0 and SPSS 23.0 were used for data analysis.One way ANOVA was used for inter group comparison, repeated measurement ANOVA was used to analyze PWT and PWL results, and Tukey test was used for pairwise comparison. Results:(1) In PWT and PWL experiments, the interaction effect between group and time, group main effect and time main effect of PWT were significant ( F=13.4, 39.6, 369.6, all P<0.05), and the interaction effect between group and time, group main effect and time main effect of PWL were significant ( F=3.8, 10.3, 58.8, all P<0.05). Compared with sham group, PWT((8.0±3.5) g, (2.4±1.4) g, (2.3±1.1) g, (2.2±1.6) g, (1.6±0.5) g) and PWL((8.6±1.3) s, (7.3±1.5) s, (7.9±1.0) s, (6.6±1.1) s, (7.7±1.4) s) in standard environment group decreased at each time point (all P<0.05). (2) Compared with sham group, the number of entrying into the central area (1.3±1.7), the time of entrying into the central area((1.6±1.3) s), the proportion of entering open arms ((8.0±7.8) %) and the proportion of time in the open arms ((1.3±1.2) %) all significantly decreased in standard environment group ( t=4.585, 5.423, 4.682, 5.202, all P<0.05). The eating latency ((365.2±94.4) s) and immobility time ((127.6±24.3) s) dramatically increased ( t=6.008, 14.290, both P<0.05). The number and time of entrying into central area of enriched environment group were both higher than those of standard environment group(both P<0.05), while the eating latency and immobility time of enriched environment group were both lower than those of standard environment group(both P<0.05). (3) Compared with sham group(CREB: (1.6±0.2), (0.8±0.5); BDNF: (0.8±0.5), (1.0±0.4)), the expression of CREB ((1.8±0.1), (1.5±0.2)), BDNF ((0.9±0.6), (1.4±0.3)) in spinal cord and ACC of standard environment group increased (spinal: t=3.283, 4.989; ACC: t=5.502, 4.257, all P<0.05). The expression of PSD-95 ((1.6±0.2), (1.0±0.2) and NLGN2 ((1.5±0.5), (1.1±0.2)) also increased in ACC of standard enviroment group ( t=4.257, 2.214, both P<0.05). Compared with standard environment group, the expression of CREB (1.3±0.3), BDNF (0.7±0.4), PSD-95(1.0±0.3) and NLGN2(1.1±0.4) in spinal cord of enriched environment group decreased ( t=5.007, 2.166, 2.358, 2.322, all P<0.05). The expression of PSD-95(1.2±0.3) and NLGN2(1.1±0.2) also decreased in ACC of enriched environment group ( t=2.674, 2.944, both P<0.05). However, the expression of p-CREB (1.7±0.6) and BDNF (2.4±0.2) increased in ACC ( t=4.180, 7.610, P<0.05). Conclusion:Enriched environment can improve neuropathic pain and anxiety- and depressive-like behavior in SNI rats, which may be related to the change of synaptic plasticity in spinal cord and ACC.

Effects and mechanisms of melatonin combined with enriched environment on learning and memory ability of SAMP8 mice / 中华行为医学与脑科学杂志

Objective:To explore the effects and possible mechanisms of melatonin combined with enriched environment on the learning and memory ability of senescence-accelerated mouse prone 8(SAMP8).Methods:Forty-eight SAMP8 male mice aged 4 months were randomly divided into model group, enriched environment group, melatonin group and melatonin combined with enriched environment group (combined intervention group) by random number table method, with 12 mice in each group. Mice in the melatonin group and combined intervention group were subcutaneously injected with melatonin at a dose of 8 mg·kg -1·d -1, and the mice in the model group and the enriched environment group were given the same amount of normal saline instead.The mice in model group and melatonin group were raised in a standard environment, and the mice in enriched environment group and combined intervention group were raised in an enriched environment.The intervention lasted 28 days. The aging degree of mice was scored before and 28 days after the intervention. Morris water maze test was used to detect the learning and memory ability of mice. Nissl staining and TUNEL staining were used to observe the Nissl staining positive cells and apoptotic cells in the CA1 area of hippocampus.ELISA was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus of mice. Western blot was used to detect the levels of amyloid β-protein (Aβ) 1-42, microtubule-associated protein tau (tau) phosphorylated at threonine (Thr) 205 (Tau pT205), Toll-like receptor 4 (TLR4), and nuclear factor-κB (NF-κB) p65 protein in the hippocampus of mice. qRT-PCR was used to detect the levels of TLR4, NF-κB p65 mRNA in the hippocampus of mice. SPSS 22. 0 statistical software was used for repeated measure ANOVA, one-way ANOVA and LSD test. Results:(1) Aging score: after intervention, the aging scores of mice in the four groups were significantly different ( F=120.601, P<0.01). The aging scores of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group (all P<0.05), while the aging score of mice in the combined intervention group was significantly lower than those in the enriched environment group and melatonin group (both P<0.05). (2) The results of the location navigation experiment showed that the time × group interaction effect of the escape latencies of mice in the four groups were significant ( F=30.524, P<0.001). From the 2nd to 4th day, the escape latencies of mice in the enriched environment group, melatonin group and combined intervention group were all lower than that in the model group (all P<0.05). The results of the space exploration experiment showed that the residence time in the target quadrant and the number of platform crossings of mice in the four groups were significantly different ( F=291.328, 113.482, both P<0.01). The residence time in the target quadrant ((29.45±1.70)s, (32.44±1.55)s, (37.48±0.84) s) and the number of platform crossings ((6.44±0.61) times, (7.16±0.70) times, (12.60±1.23) times) of mice in the enriched environment group, melatonin group and combined intervention group were higher than those in the model group ((15.07±1.28) s, (4.10±0.61) times), while the residence time in the target quadrant and the number of platform crossings of mice in the enriched environment group and the melatonin group were significantly lower than those in the combined intervention group (all P<0.05). (3) Nissl and TUNEL staining showed that the number of Nissl positive neurons in the hippocampal CA1 region of mice in the four groups were significantly different ( F=809.264, P<0.01), and the number of apoptotic cells in the hippocampal CA1 region were also significantly different ( F=1 060.583, P<0.01). The number of Nissl stained positive neurons in the hippocampal CA1 region of mice in the combined intervention group was more than those in the model group, enriched environment group, and melatonin group (all P<0.05), and the number of apoptotic cells were less than those in the model group, enriched environment group, and melatonin group (all P<0.05). (4) The results of ELISA assay showed that there were significantly different in the levels of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the four groups ( F=152.887, 63.506, 432.026, all P<0.01). The contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group(all P<0.05). Among them, the contents of IL-1β, IL-6 and TNF-α in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (5) Western blot analysis showed that there were significantly different in the protein expression levels of Aβ1~42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the four groups ( F=122.349, 98.934, 201.635, 116.553, all P<0.01). The protein expression levels of Aβ1-42, tau pT205, TLR4, and NF-κB p65 in the hippocampus of mice in the enriched environment group, melatonin group, and combined intervention group were lower than those in the model group.Among them, the protein expression levels of Aβ1-42, tau pT205, TLR4, NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). (6) qRT-PCR showed that the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the four groups were significantly different ( F=42.913, 102.446, both P<0.01). The mRNA expression levels of TLR4 ((0.63±0.05), (0.55±0.04), (0.42±0.03)) and NF-κB p65 ((0.98±0.06), (0.82±0.04), (0.72±0.04)) in the hippocampus of mice in the enriched environment group, melatonin group and combined intervention group were lower than those in the model group ((0.74±0.07), (1.20±0.05)) (all P<0.05). Among them, the mRNA expression levels of TLR4 and NF-κB p65 in the hippocampus of mice in the enriched environment group and melatonin group were significantly higher than those in the combined intervention group (all P<0.05). Conclusion:Melatonin combined with enriched environment can improve the learning and memory ability and neuroinflammatory response of SAMP8 mice, and its mechanism may be related with the down-regulation of TLR4/NF-κB p65 signaling pathway.

Oxygen-enriched Environment Established by Hydrogen Peroxide Eradicates Helicobacter pylori in vitro and in vivo / 胃肠病学

Background: Eradication of Helicobacter pylori (Hp) effectively is becoming exceedingly challenging due to the increase in antibiotic resistance and recurrence of Hp infection. Aims: To explore the effect of an oxygen-enriched environment established by hydrogen peroxide (H

The mechanism of enriched environment repairing the learning and memory impairment in offspring of prenatal stress by regulating the expression of activity-regulated cytoskeletal-associated and insulin-like growth factor-2 in hippocampus

BACKGROUND@#Prenatal stress can cause neurobiological and behavioral defects in offspring; environmental factors play a crucial role in regulating the development of brain and behavioral; this study was designed to test and verify whether an enriched environment can repair learning and memory impairment in offspring rats induced by prenatal stress and to explore its mechanism involving the expression of insulin-like growth factor-2 (IGF-2) and activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus of the offspring.@*METHODS@#Rats were selected to establish a chronic unpredictable mild stress (CUMS) model during pregnancy. Offspring were weaned on 21st day and housed under either standard or an enriched environment. The learning and memory ability were tested using Morris water maze and Y-maze. The expression of IGF-2 and Arc mRNA and protein were respectively measured by using RT-PCR and Western blotting.@*RESULTS@#There was an elevation in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy. Maternal stress's offspring exposed to an enriched environment could decrease their plasma corticosterone level and improve their weight. The offspring of maternal stress during pregnancy exhibited abnormalities in Morris water maze and Y-maze, which were improved in an enriched environment. The expression of IGF-2, Arc mRNA, and protein in offspring of maternal stress during pregnancy was boosted and some relationships existed between these parameters after being exposed enriched environment.@*CONCLUSIONS@#The learning and memory impairment in offspring of prenatal stress can be rectified by the enriched environment, the mechanism of which is related to the decreasing plasma corticosterone and increasing hippocampal IGF-2 and Arc of offspring rats following maternal chronic stress during pregnancy.

Effects of Enriched Environment on Cognition and Expression of Bcl-2/Bax Protein in Hippocampus after Ischemic Stroke in Mice / 中国康复理论与实践

Objective:To explore the effect of enriched environment on spatial learning and memory of mice after ischemic stroke and the expression of apoptotic regulatory protein Bcl-2 and Bax in hippocampus. Methods:Clean grade adult male C57BL/6 mice (n = 42) were occluded left middle cerebral artery permanently. Three days after operation, the modeling mice were randomly divided into standard group (n = 16) and enriched environment group (n = 16). Other eight mice were as sham group. The sham group and the standard group were fed in standard environment, while the enriched group was fed in enriched environment. They were tested with Morris Water Maze 21 days after intervention, and the expression of Bcl-2 and Bax protein in hippocampus was detected with Western blotting and immunofluorescence staining. Results:The latency was less in the enriched group than in the standard group (P < 0.05), and the time and swimming distance staying in the target quadrant were more (P < 0.05), as well as the times crossing the target quadrant (P < 0.05). Compared with the standard group, the expression of Bcl-2 increased in the enriched group, while the expression of Bax decreased (P < 0.05). Conclusion:Enriched environment can improve the spatial learning and memory of mice after ischemic stroke, which may be associated with reducing apoptosis in hippocampus.

Enriched environment improves sevoflurane-induced cognitive impairment during late-pregnancy via hippocampal histone acetylation

Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.

Protective Effect of Environmental Enrichment on the Morphology of Neurons in the Motor Cortex of Diabetic and Stressed Rats

Background:The present study aimed to evaluate the effects of EE on the morphology of pyramidal neuron at the motor cortex of diabetic and stressed rats.Methods and materials:Male Wistar rats were grouped into Normal Control (NC), Vehicle Control (VC), Diabetes (D), Diabetes + Stress (D+S), Diabetes + Environmental Enrichment (D+EE) and Diabetes + Stress +Environmental Enrichment (D+S+EE) (n=8). Hyperglycemia was induced in Westar rats using streptozotocin (40mg/kg; ip). Blood sugar levels and body weight was measured at regular intervals to monitor the development of hyperglycemia. All experimental groups were housed in standard cages throughout the experiment. Rats in groups D+S and D+S+EE were transferred into space restrained cages for 6 hours daily. D+S+EE group were transferred into EE cages immediately after the space restrained session for subsequent 6 hours daily. On day 30, all rats were sacrificed and brains were harvested and prepared for rapid Golgi staining protocol. Dendritic branchings and dendriticintersections of the motor cortex neurons were quantitated using a camera lucida attached to Biolux research microscope. Data was analyzed using ANOVA with Bonferroni’s test.

Neuronal Remodeling and Dendritic Spines: A Review

The neurons show remodeling in their dendritic arbor and spine/synapsenumber in many brain regions including the hippocampus, amygdala and the prefrontalcortex. The dendritic spine density is reported to be changed due to experiences andstressful conditions. The dendritic spines are the small protrusions arising from thedendritic shaft of the neurons. They have basic shapes as large mushroom spines, shortstubby spines and thin spines. The morphology of spines changes rapidly in response tovarious stimuli that may be internal such as hormones and external such as environmentalchanges. Dendritic spine density plays a major role in classification of principal neuronsi.e. multipolar and pyramidal neurons. The principal neurons may be classified as sparselyspinous, moderately spinous and heavily spinous on the basis of density of spine over thedendritic branches. In response to environment dendritic remodeling takes place in theform of spine shapes, spine turnover and spine density etc. Synaptic plasticity primarilytakes place in dendritic spines and enriched environment have positive effect while socialisolation have negative effect on synapse formation. Exposure of animals to environmentalcomplexity may improve the learning and memory by providing adaptive changes in thedendritic spine density.

Effects of enriched environment on the subunits N-mehyl-D-aspartate receptors at the 17th area of the visual cortex in adult amblyopia rats / 中华实验眼科杂志

Objective To explore the effect of enriched environment on the level of NR2A and NR2B subunits of N-mehyl-D-aspartate (NMDA) receptors which belong to glutamate receptors with excitability at the 17th area of the visual cortex in amblyopia rats after the critical period,and to understand the possible mechanism of synaptic plasticity of the visual cortex in adult amblyopia rats.Methods Eighty Wistar rats were divided into normal group and experimental group by random number table.Right eyelids of all rats were sutured through the whole critical period in order to establish monocular deprivation (MD) amblyopia model.The rats in experimental group were divided into the amblyopia group,standard environment (SE) group and environmental enrichment (EE) group on P45 in random.The sutured right eyelids were opened on P46 in the SE group and EE group.All rats were sacrificed to get the 17th area of the left visual cortex on P60,P75 and P105.Three rats were used at different time points from each group.The Ⅰ-Ⅵ layers of the visual cortex area 17 were observed by using hematoxylin-eosin staining.The expression of NMDA-NR2A and NMDA-NR2B was detected by immunohistochemistry.Integrated optical density of NMDA-NR2A and NMDA-NR2B was detected by using special image analysis software (Image-Pro Plus 6.0).The use of animals complied with Regulation on the Managenment Experimental Ainimals from Shandong Eye Institute and Association for Research in Vision and Ophthalmology (ARVO).Results The positive expression of NMDA-NR2A and NMDA-NR2B were observed in the visual cortex.The positive cells were mostly round or elliptical and mainly expressed in cell membrane.The expression of NMDA-NR2A in P60,P75 and P105 from four groups had statistical differences (all at P＜0.05).There were less positive cells in amblyopia group and EE group than normal control group on P60,P75 and P105,while there were more positive cells in EE group than amblyopia group.Amblyopia can lead to reduced NMDA-NR2A expression in the visual cortex.The expression of NMDA-NR2A was stronger than that in the amblyopia group by intervention 15 days,30 days,and 60 days with the rich environments,but did not reach the normal level (all at P＜0.05).The expression of NMDA-NR2B in P60,P75 and P105 from four groups also had statistical difference (all at P＜0.05).There were more positive cells in amblyopia group than those in normal control group on P60,P75 and P105.There were more positive cells in EE group than normal control group on P60,while there were equal positive cells in EE group and normal control group on P75 and P105.Amblyopia can lead to increase NMDA-NR2B expression in the visual cortex.The expression of NMDA-NR2B was weaker than that in the amblyopia group by intervention 15 days with the rich environments,but did not reach the normal level (all at P＜ 0.05).The expression of NMDA-NR2B after intervention 30 days and 60 days reached the normal levels (all at P＞ 0.05).Conclusions The plasticity of visual cortex exists not only in the critical period but also after the critical period of visual development.EE,as a non-invasion method,can improve and recover the synaptic plasticity in visual cortex of adult rats by the expression of NMDA-NR2A and NMDA-NR2B.

Influence of enriched environment on visual function and synaptic plasticity in adult amblyopic mice / 中华实验眼科杂志

Objective To examine role and possible mechanism of enriched environment (EE) on regulating recovery of visual function in adult monocular deprivation amblyopia mice.Methods A total of 72 healthyKunming mice were divided into normal control group,monocular deprivation (MD) group,MD+EE group and M D+ fluoxetine group by random number table.Except for the normal control group,the mice in the other groups were sutured on the right eyelid 21 days after birth to establish MD amblyopia model.the mice were fed in standard environment or EE for 4 weeks according to the group.Visual acuity and flash visual evoked potential (F-VEP) of mice in each group were detected.The distribution of microtubule associated protein 2 (MAP2) in visual cortex of adult amblyopic mice were detected by immunohistochemistry.The expression of MAP2,synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) protein in visual cortex of adult amblyopic mice were detected by western blot.The experimental protocol was approved by the Animal Care and Use Committee of Hunan Children's Hospital and conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals.Results There was a significant difference in the visual acuity of deprived eye among each group (F=114.632,P＜0.001).The visual acuity in MD group is lower than that in normal control group,with a significant difference (t =15.480,P＜0.001).Compared with MD group,visual acuity was restored in MD+ EE group and MD +fluoxetine group,with significant differences (t =15.071,P ＜ 0.001;t =14.841,P ＜ 0.001).There was a significant difference in the P2 latency and amplitude of F-VEP in deprived eye among each group (F=36.510,P=0.000;F=34.140,P=0.000).Compare with normal control group,P2 latency was prolonged and P2 amplitude of F-VEP was decreased in deprived eye in MD group,with significant differences (t =10.220,P =0.000;t =10.09,P =0.000).Western blot assay showed that there was a significant difference in the expression of MAP2 in visual cortex contralateral deprived eye among each group (F=18.142,P=0.000).The expression of MAP2 in MD group was significantly lower than that in normal contral group (t=3.056,P＜0.01);Compared with MD group,MAP2 expression was increased in MD+EE group and MD+fluoxetine group (t =2.541,P =0.031;t =2.157,P =0.017).There were significant differences in the expression of SYP and PSD-95 in visual cortex contralateral to deprived eye among each group (F =12.871,P =0.000;F =25.060,P =0.000).Compared with normal contral group,SYP and PSD-95 expression in visual cortex were down-regulated in MD group,with significant differences (t =6.054,P =0.000;t =8.631,P =0.000).The expression of SYP and PSD-95 protein in MD+EE group and MD+fluoxetine group were significantly higher than those in MD group (all at P＜0.05).Conclusions EE can recover visual function through up-regulating the expression of MAP2,which can modulate the dendritic branch trim and neural plasticity of visual cortex in adult MD mice.

Advance in Basic Researches about Enriched Environment for Neuropathic Pain (review) / 中国康复理论与实践

Neuropathic pain is a common health problem in clinic. The enriched environment can increase the threshold of pain in models of neuropathic pain, which may associate with the alleviation of inflammation and excitability of nerves.

Effects of Enriched Environment on Apoptosis and Brain-derived Neurotrophic Factor /Tyrosine Kinase Receptor B Signaling Pathway in Hippocampal Neurons of Neonatal Rats with Hypoxic-ischemic Brain Damage / 中国康复理论与实践

Objective:To investigate the effects of enriched environment on hippocampal neuronal apoptosis and brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway in neonatal rats with hypoxic-ischemic brain damage. Methods:Forty-eight newborn Wistar rats aged seven days were randomly divided into sham operation group, model group and enriched environment group, each group was divided in to 14 days group and 28 days group, with eight in each subgroup. The model was established with the Rice method. The sham operation group and the model group did not receive any intervention, and the enriched environment group received enriched environment stimulation 24 hours after modeling. Fourteen days and 28 days after modeling, the levels of neuronal apoptosis in hippocampus were detected by TUNEL and double immunofluorescence staining; BDNF and TrkB proteins in hippocampus were detected by immunohistochemical staining. Results:Fourteen days and 28 days after modeling, the numbers of TUNEL positive cells, double immunofluorescence positive cells, BDNF and TrkB positive cells were significantly more in the model group than in the sham operation group (t > 27.214, P < 0.001), while the numbers of TUNEL positive cells, double immunofluorescence positive cells were significantly less in the enriched environment group than in the model group (t > 12.687, P < 0.001); and the number of BDNF and TrkB positive cells were significantly more in the enriched environment group than in the model group 28 days after modeling (t > 137.998, P < 0.001). Conclusion:Enriched environmental stimulation could reduce the apoptosis of hippocampal neurons, and up-regulate the expression of BDNF and TrkB proteins in the neonatal rats with hypoxic-ischemic brain damage.

Educando en un ambiente enriquecido: porque todos estamos conectados / Educating in an enriched environment: because we are all connected

El objetivo de esta revisión es dar a conocer las diferentes vertientes que sustentan el proceso del aprendizaje en base a un concepto que ha alcanzado una gran importancia en los últimos años, el Ambiente Enriquecido (AE). Un término que ha sido emanado desde la biología, con diversos estudios de laboratorio realizados por científicos de renombre mundial y que, progresivamente ha ido incorporándose a disciplinas como la Psicología y la Pedagogía. En este artículo proponemos la descripción del impacto de este concepto en el proceso de aprendizaje experimentado por los seres humanos y su abordaje desde una perspectiva multidisciplinaria. Comenzamos por describir las bases neurofisiológicas del aprendizaje, con los fundamentos de la teoría neuronal como principal protagonista, pasando por la importancia de la Plasticidad Sináptica (PS) en el proceso de aprendizaje, el fenómeno de la Potenciación a Largo Plazo (PLP), como proceso generador de redes neuronales efectivas y sólidas. Posteriormente abordamos la génesis del Ambiente Enriquecido, con su origen en los experimentos con ratones de laboratorio, para posteriormente describir los conceptos y términos que han emanado del mismo que han sido aplicables a la Psicología Educacional tales como el Ambiente Desafiante, los instrumentos necesarios para su implementación y también el importante rol de las emociones en el proceso de aprendizaje de los sujetos. Finalmente, describimos el rol de la Pedagogía en la aplicación de actividades efectivas que conduzcan a un aprendizaje significativo en base al Ambiente Enriquecido.

The aim of this review is to present different strands that sustain the learning process based on a concept that has reached a major importance in recent years, the Enriched Environment (EE). A term that has been emerged from biology, with various laboratory studies conducted by world-renowned scientists and that has progressively been incorporated into disciplines such as Psychology and Education. In this article, we propose the description of the impact of this concept on the learning process experienced by human beings and its approach from a multidisciplinary perspective. We begin by describing the neurophysiological bases of learning, with the fundamentals of neuronal theory as the main protagonist, passing through the importance of Synaptic Plasticity (SP) in the learning process, the phenomenon of Long Term Potentiation (LTP), as a generating process of effective and solid neural networks. Subsequently, we covered the genesis of the Enriched Environment, with its origin in the experiments with laboratory mice, to later describe the concepts and terms that have emanated from it and have been applicable to Educational Psychology, such as Challenging Environment, the necessary instruments for its implementation and the important role of emotions in the subjects' learning process. Finally, we describe the role of Education in the implementation of effective activities that lead to meaningful learning based on the Enriched Environment.

Advance of Enriched Environment in Neural Plasticity post Hypoxic-ischemic Brain Damage (review) / 中国康复理论与实践

@#The enriched environment is an artificial environment for animal models of rodentia. In the enriched environment, model animals may improve synaptic plasticity, inhibit apoptisis and regulate autophage after hypoxic-ischemic brain damage, that promote the recovery.