Environmental enrichment ameliorates the impairments of a rodent model of prodromal Parkinson's disease.

Functional and morphological alterations in animal models of valproic acid exposure.

Aging remodels hippocampal transcriptional architecture by upregulating neuroinflammatory gene programmes and suppressing neuronal and metabolic networks, increasing ischemic injury susceptibility. Environmental enrichment (EE), a non-pharmacological intervention known to promote brain plasticity, has not previously been assessed at a systems level against aging- and stroke-associated co-expression programmes. Weighted gene co-expression network analysis (WGCNA) was applied to hippocampal RNA-seq data (GSE302188), yielding 45 modules, 24 of which were significantly age-associated (FDR < 0.05). Ten Age-UP modules were enriched for neuroinflammatory and immune activation pathways, nine Age-DOWN modules showed heterogeneous profiles including ribosomal RNA processing, and nominal enrichment for synaptic organisation pathways. Gene set enrichment analysis against an independent stroke dataset (GSE137482) identified 29 stroke-engaged modules (FDR < 0.05-0.25), 18 of which were Age-Neutral, indicating largely distinct aging and stroke transcriptional signatures. Cell-type deconvolution using MuSiC confirmed that age-associated module trajectories reflect coordinated within-cell transcriptional reprogramming rather than shifts in hippocampal cellular composition. In young adult mice (GSE95740; 3 months), EE did not preferentially reverse the concordantly dysregulated aging-stroke modules. To evaluate EE effects on established aging programmes, module eigengenes from an independent aged dataset (PRJEB58981;17 months) were projected onto the aging reference trajectory. EE partially opposed age-suppressed co-expression programmes but did not suppress the neuroinflammatory (turquoise) or interferon (sienna3) modules most strongly implicated in the aging-stroke overlap. Collectively, EE engaged hippocampal co-expression architecture principally through plasticity- and glial-related mechanisms. These findings identify complement and interferon signalling as priority targets for adjunctive pharmacological strategies in aged stroke-vulnerable populations. Adequately powered studies comparing young and aged animals across EE, stroke, and combined EE-plus-stroke conditions are required to determine EE's potential to suppress the concordant aging-stroke immune substrate represents a fundamental biological boundary or a tractable target in age-matched experimental designs.

Adolescent experiences remodel hippocampal glycerophospholipid metabolism associated with adult memory.

Revisiting Obstetric Brachial Plexus Injuries Through a Central Nervous System Lens: Toward Integrated Diagnostic and Therapeutic Frameworks.

Impact of physical and sensory enrichment on the physiological status and disease resistance of triploid rainbow trout (Oncorhynchus mykiss)

Environmental enrichment modulates the mouse immune system.

Endogenous neuroprotection in vascular cognitive impairment and dementia.

Environmental enrichment suppresses colorectal cancer progression with comorbid depression by modulating the immunosuppressive tumor microenvironment.

ABSTRACT Parrots are among the most popular pets, yet few studies have examined how guardians provide their birds with environmental enrichment (EE). This study described common EE practices, identified underutilized strategies, documented behavior problems, and explored guardian motivations using a global online survey (n = 619, November 2020–February 2021). Most participants had heard of EE (88.8%), and nearly all reported intentionally providing it once defined (98.8%). Common practices included varying diet, rotating toys, encouraging bathing, and facilitating social interactions, however, diet-based enrichment often raised nutritional concerns. Fewer than half of parrots received cardiovascular exercise via flight (48.9%), foraging-based activities (46.2%), or positive reinforcement training (34.6%). Human interaction was commonly perceived as the most preferred EE by birds, followed by food-based and destructible toys. Guardian age was associated with EE motivations (χ², p = 0.034 to <0.001), with younger guardians more commonly citing welfare-related reasons. Most guardians (65.4%) reported at least one behavior concern, with aggressive and compulsive behaviours frequently being co-reported with fearfulness. Together these findings provide a foundation for evidence-based strategies to promote companion parrot welfare.

Amylovis-201 (CNEURO-201) shows strong neuroprotective activity in Alzheimer's disease (AD) models due to its anti-Aβ aggregating properties and sigma-1 receptors (S1R) agonist activity. The drug is neuroprotective in transgenic rodent models of AD that could translate into disease-modifying effects by both protecting neuronal and glial viability and actively decreasing amyloid aggregation. The individual vulnerability to the neurodegenerative process in AD is highly dependent on the "cognitive reserve," understood as the efficacy of brain plasticity throughout lifetime events. We aimed to determine whether Amylovis-201 efficacy in AD could be potentiated through stimulation of cognitive reserve. We combined Amylovis-201 administration with an experimental model of environmental enrichment (EE), using training on the Hamlet device. We analyzed the potentiating effects of the combination on brain plasticity and the development of resilience against memory deficits in a pharmacological AD model. We implemented a combined protocol with repeated per os (PO) administration of Amylovis-201 (0.1 and 1 mg/kg) and EE over 2 weeks (5 days/week), consisting of a 4-hour exploration of the Hamlet, a complex environment mimicking a small village with five functionalized houses. The combination of EE and low dose (0.1 mg/kg PO) of Amylovis-201 had an additive effect on hippocampal neurogenesis. It also protected mice against scopolamine (0.5 mg/kg IP)-induced spatial working memory deficits in the Y-maze and, at 0.1 or 1 mg/kg PO, against Aβ25-35-induced memory deficits. As EE is known to increase S1R expression, the combination of EE and Amylovis-201 had major effects on brain plasticity and neuroprotection.

Strength training induces ABHD5-ATGL axis to counteract mesenteric fat accumulation in obese Swiss mice.

Neonatal exposure to sevoflurane has been implicated in long-term neurodevelopmental abnormalities, yet the underlying mechanisms remain unresolved. This study sought to determine whether cGAS-STING-mediated microglial activation and aberrant synaptic pruning underlie sevoflurane-induced cognitive deficits and to assess how environmental conditions modulate these processes. Neonatal mice underwent sevoflurane exposure followed by rearing in enriched (EE) or impoverished (IE) environments. Cognitive function, synaptic structure, microglial activity, mitochondrial status, and cGAS-STING signaling were evaluated using behavioral tests, immunostaining, biochemical assays, and pharmacological inhibition. Sevoflurane exposure induced cognitive impairment, microglial overactivation, mitochondrial dysfunction, and excessive synaptic pruning resulting from microglial overactivation. EE mitigated these abnormalities by preserving mitochondrial integrity and reducing mtDNA-driven cGAS-STING activation, thereby preventing the microglia-mediated imbalance in synaptic pruning and improving cognitive outcomes. In contrast, IE exacerbated mitochondrial injury, aggravated synaptic loss, and further worsened cognitive impairment. Sevoflurane disrupts neurodevelopment through a mitochondria-cGAS-microglia-synapse pathway. Environmental enrichment offers significant neuroprotection, highlighting both cGAS-STING signaling and early-life environmental modulation as promising targets for preventing anesthesia-related neurodevelopmental injury.

Combined environmental enrichment and aerobic exercise improve cognitive recovery in male rats after bilateral common carotid artery occlusion.

Mining activities cause soil heavy metal accumulation, nutrient imbalance, and ecological degradation. Bryophytes, as pioneer plants, have potential for ecological indication and heavy metal enrichment, yet their response mechanisms to environmental gradients in mining areas remain unclear. We investigated five functional zones in a typical lead-zinc mining area of Southwest China's karst region, using NMDS, CCA, Mantel tests, PLS‑PM to elucidate relationships among soil environment, bryophyte community, functional traits, and heavy metal enrichment. Soil heavy metal concentrations ranked: ore washing area > mining area > ore stockpiling area > waste rock area > control area. Soil TOC, TN, and pH were negatively correlated with heavy metals. We recorded 48 bryophyte species (29 genera, 11 families), dominated by Pottiaceae and Bryaceae. In polluted areas, bryophyte richness and functional diversity were significantly reduced (P < 0.05) and negatively correlated with heavy metals. Bryophytes selectively enriched As, Cd, Zn, and Pb (P < 0.05); As, Cd, and Zn were highest in the ore washing area, while Pb was high in ore washing and mining areas. Under heavy metal stress, defensive traits (long rhizoids, leaf papillae, high antioxidant activity) dominated, whereas growth‑related traits (large leaf area, tall shoots, high chlorophyll) prevailed in the control area. PLS‑PM revealed that species diversity negatively affected enrichment, whereas functional diversity positively regulated it. This study elucidates trait‑mediated mechanisms of bryophyte adaptation and heavy metal enrichment, providing a theoretical basis for ecological restoration in mining areas.

The claudin-5 (CLDN5) gene is critical for blood brain barrier integrity and may link traumatic stress, accelerated aging, and neurological disease. Building on prior research showing associations between trauma exposure and PTSD with CLDN5 DNA methylation (DNAm), we tested if candidate CLDN5 DNAm loci were associated with advanced epigenetic aging in blood and brain tissue and with hippocampal volume. 1302 trauma-exposed individuals (Mage=44.23, SD=13.71; 76% male) underwent psychiatric diagnostic interviews and blood draws for obtaining epi/genetic information; 473 underwent magnetic resonance imaging of the brain. Data from 109 PTSD brain bank decedents with DNAm from ventromedial prefrontal cortex (vmPFC) were also examined (Mage-at-death=45.20, SD=14.21; 62% male). All candidate loci were associated with metrics of epigenetic age in blood (p-adj range: .0396 to 4.5e-05) and these associations largely extended to postmortem vmPFC. There was an indirect association between PTSD severity and CLDN5 DNAm in blood at cg21872764 via GrimAge residuals (indirect β=.033, P=.040) that was diminished when the direct PTSD association was modeled. The CLDN5 probe cg17411190 in blood was negatively related to left and right hippocampal volume (p-adj=.042) and with volume of multiple hippocampal substructures. The association between PTSD severity and hippocampal volume was indirect via blood DNAm at cg17411190 (indirect β=-.011, P=.045). PTSD severity-related accelerated aging may be associated with altered CLDN5 DNAm, which may signal neurodegeneration, such as reduced hippocampal volume. CLDN5 DNAm in blood may serve as a useful proxy for brain CLDN5 DNAm. Given that prior environmental enrichment and antidepressant studies show initial efficacy in altering CLDN5 expression, future studies could evaluate if PTSD treatment alters CLDN5 epigenetics and reduces risk for neurodegeneration.

Effects of environmental enrichment on cocaine addiction-related behaviors in rodents: A systematic review and meta-analysis.

ObjectiveThis study evaluated whether quantitative electroencephalography (QEEG) guided neurofeedback (NF) improves intellectual functioning and attention in children with mild to severe intellectual disability (ID).MethodsSixty-five children (38 males, 27 females; mean age ≈11 years) with DSM-5 diagnoses of mild-to-severe ID (IQ 28-68) and histories of unsuccessful standard treatments were enrolled. Baseline assessments included 19-channel QEEG referenced to FDA-approved Nx-Link™, BrainDx™, and NeuroGuide™ databases, Wechsler Intelligence Scale for Children (WISC-R or WISC-IV),and the Test of Variables of Attention (TOVA). Participants underwent 80-120 QEEG-guided NF sessions. Training protocols targeted deviant z-scores, with hypercoherence addressed prior to amplitude abnormalities. IQ and attention were reassessed 6-12 months post-treatment. Outcomes were analyzed using paired t-tests, correlation analyses, and generalized linear models.ResultsMean full-scale IQ increased by approximately 10 points (≈53 to ≈63; +18.6%, p < 0.001). Significant gains were observed in both WISC-IV (+≈11 points) and WISC-R (+≈10 points), with improvements across verbal, perceptual, working memory, processing speed, and performance domains (all p < 0.001). Two thirds of participants' IQ increased by ≥6 points. TOVA scores improved but were not correlated with IQ changes. QEEG analyses showed normalization of resting-state networks, including increased alpha power in default mode network hubs and reduced coherence and phase lag; reductions in slow-wave coherence predicted IQ improvement.ConclusionQEEG-guided NF was associated with clinically meaningful improvements in intellectual functioning and attention in children with ID, exceeding gains expected from environmental enrichment. Findings support NF as a promising nonpharmacologic intervention warranting randomized controlled trials.

Learning broadly alters neocortical synapses, although the input and target specificity for this plasticity has not been well-defined. Feedforward synapses into sensory cortex have early critical periods for plasticity after which they are resistant to experience-dependent changes. Whether these synapses are altered during learning has not been investigated, particularly in a setting where animals must identify causal relationships between sensory stimuli and rewards. Here, we examined whether these feedforward synapses can be altered by training mice in a freely-moving and whisker-dependent association task. Pathway-specific optogenetic stimulation and analysis of quantal excitatory postsynaptic currents in layer 2/3 (L2/3) pyramidal neurons from barrel cortex revealed a rapid and transient potentiation of layer 4 (L4) inputs at the onset of training, without any change in thalamocortical inputs onto L4 neurons. In contrast, pseudotraining—where stimuli and rewards were decoupled—drove depression of L4–L2/3 quantal excitatory postsynaptic currents. Because environmental enrichment did not influence quantal excitatory postsynaptic current amplitude, these data suggest that reward-prediction accuracy is a key driver of feedforward plasticity in primary sensory cortex.Significance statementAlthough it is well accepted that sensory learning can alter cortical synapses, the pathways that are modified and the specific cues that drive this synaptic change have not been systematically investigated. By manipulating stimulus–reward probabilities, we identified discrete and opposite changes in the strength of L4–L2/3 synapses depending on the predictive accuracy of the stimulus. These data suggest that feedforward sensory circuits are exquisitely sensitive to the predictive value of sensory input in a goal-directed task.

Medical education is transforming due to new technologies such as artificial intelligence (AI). Although AI is being considered for medical education, its integration into the curriculum remains limited. Furthermore, few studies evaluate how these tools affect students' diagnostic accuracy during clinical rotations. This study aims to evaluate available evidence regarding AI tools in medical students, identifying their effects on clinical education and clinical decision-making, as well as their implications for medical practice during clinical rotations. For this purpose, a scoping review was conducted in December 2025. The literature search was performed across key databases using MeSH and DeCS terms. Studies published between 2015 and 2025 were included.After screening, 26 articles were included. Most studies suggest a positive effect of AI on students' clinical education and clinical decision-making, particularly in solving clinical cases and interpreting images. AI appears to support students in reaching performance levels closer to experienced physicians, which could influence medical care quality. Seven articles reported a neutral effect, warning that incorrect or unclear AI responses might cause confusion. In conclusion, this review suggests that AI may have a positive effect on medical students, especially those with less clinical experience, potentially bringing them on par with more experienced professionals. The need for structured AI integration into the curriculum is underscored, as it has the potential to improve academic performance and provide enriched learning environments. However, ensuring adequate training and regulation for its efficient use is key to addressing the associated ethical and legal implications in healthcare settings.