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Enriched environment causes epigenetic changes in hippocampus and improves long-term cognitive function in sepsis. Scientific reports Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory response. Environmental conditions play an important role in various pathologies depending on the stimulus it presents. A standard environment condition (SE) may offer reduced sensory and cognitive stimulation, but an enriched environment improves spatial learning, prevents cognitive deficits induced by disease stress, and is an important modulator of epigenetic enzymes. The study evaluated the epigenetic alterations and the effects of the environmental enrichment (EE) protocol in the brain of animals submitted to sepsis by cecal ligation and perforation (CLP). Male Wistar rats were divided into sham and CLP at 24 h, 72 h, 10 days and 30 days after sepsis. Other male Wistar rats were distributed in a SE or in EE for forty-five days. Behavioral tests, analysis of epigenetic enzymes:histone acetylase (HAT), histone deacetylase (HDAC) and DNA methyltransferase (DNMT), biochemical and synaptic plasticity analyzes were performed. An increase in HDAC and DNMT activities was observed at 72 h, 10 days and 30 days. There was a positive correlation between epigenetic enzymes DNMT and HDAC 24 h, 10 days and 30 days. After EE, HDAC and DNMT enzyme activity decreased, cognitive impairment was reversed, IL1-β levels decreased and there was an increase in PSD-95 levels in the hippocampus. Interventions in environmental conditions can modulate the outcomes of long-term cognitive consequences associated with sepsis, supporting the idea of the potential benefits of EE. 10.1038/s41598-022-14660-6
An enriched environment improves maternal sleep deprivation-induced cognitive deficits and synaptic plasticity via hippocampal histone acetylation. Brain and behavior INTRODUCTION:Growing evidence clearly demonstrates that maternal rodents exposure to sleep deprivation (SD) during late pregnancy impairs learning and memory in their offspring. Epigenetic mechanisms, particularly histone acetylation, are known to be involved in synaptic plasticity, learning, and memory. We hypothesize that the cognitive decline induced by SD during late pregnancy is associated with histone acetylation dysfunction, and this effect could be reversed by an enriched environment (EE). METHODS:In the present study, pregnant CD-1 mice were exposed to SD during the third trimester of pregnancy. After weaning, all offspring were randomly assigned to two subgroups in either a standard environment or an EE. When offspring were 3 months old, the Morris water maze was used to evaluate hippocampal-dependent learning and memory ability. Molecular biological techniques, including western blot and real-time fluorescence quantitative polymerase chain reaction, were used to examine the histone acetylation pathway and synaptic plasticity markers in the hippocampus of offspring. RESULTS:The results showed that the following were all reversed by EE treatment: maternal SD (MSD)-induced cognitive deficits including spatial learning and memory; histone acetylation dysfunction including increased histone deacetylase 2 (HDAC2) and decreased histone acetyltransferase (CBP), and the acetylation levels of H3K9 and H4K12; synaptic plasticity dysfunction including decreased brain-derived neurotrophic factor; and postsynaptic density protein-95. CONCLUSIONS:Our findings suggested that MSD could damage learning ability and memory in offspring via the histone acetylation pathway. This effect could be reversed by EE treatment. 10.1002/brb3.3018
Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus. Nature communications Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and transcriptome data sets from mouse dorsal and ventral DG. We find genome-wide transcriptional and methylation differences between dorsal and ventral DG, including at key developmental transcriptional factors. Peripubertal environmental enrichment increases hippocampal volume and enhances dorsal DG-specific differences in gene expression. Enrichment also enhances dorsal-ventral differences in DNA methylation, including at binding sites of the transcription factor NeuroD1, a regulator of adult neurogenesis. These results indicate a dorsal-ventral asymmetry in transcription and methylation that parallels well-known functional and anatomical differences, and that may be enhanced by environmental enrichment. 10.1038/s41467-017-02748-x
Temporal effects of environmental enrichment-mediated functional improvement after experimental traumatic brain injury in rats. Matter Ashley M,Folweiler Kaitlin A,Curatolo Lauren M,Kline Anthony E Neurorehabilitation and neural repair BACKGROUND:Environmental enrichment (EE) enhances motor and cognitive performance after traumatic brain injury (TBI). However, whether the EE-mediated benefits are time dependent and task specific is unclear. A preliminary study, in which only half of the possible temporal manipulations were evaluated, revealed that the beneficial effects of enrichment were only observed when provided concurrently with specific training (ie, motor or cognitive), suggesting task-specific dependence. OBJECTIVE:To further assess the effects of time of initiation and duration of EE on neurobehavioral recovery after TBI by evaluating and directly comparing all the temporal permutations. METHODS:Anesthetized adult male rats received either a cortical impact or sham injury and were then randomly assigned to 8 groups receiving continuous or early and delayed EE with either 1 or 2 weeks of exposure. Functional outcome was assessed with established motor (beam-balance/walk) and cognitive (Morris water maze) tests on postinjury days 1 to 5 and 14 to 18, respectively. RESULTS:Motor ability was enhanced in the TBI groups that received early EE (ie, during testing) versus standard housing. In contrast, acquisition of spatial learning was facilitated in the groups receiving delayed EE (ie, during training). CONCLUSIONS:These data support the conclusion from the previous study that EE-mediated functional improvement after TBI is contingent on task-specific neurobehavioral experience and extends those preliminary findings by demonstrating that the duration of enriched exposure is also important for functional recovery. 10.1177/1545968310397206