Search Results (1,708)

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders worldwide and is characterized by progressive memory impairment, cognitive decline, and behavioral dysfunction. The brain’s high energy demand makes it vulnerable to hypoxia, which can trigger AD pathology. Hypoxia-inducible factor (HIF) is a transcription factor that mediates cellular and tissue adaptation to low oxygen levels. HIF-1 plays a dual role in AD: on the one hand, it is considered a potential neuroprotective target; on the other hand, its activation may exacerbate disease pathogenesis by promoting amyloid plaque formation. Given this ambiguity, further studies are needed. This study investigated the HIF prolyl hydroxylase inhibitor Roxadustat in 6-month-old male 5xFAD mice. Stabilization of the HIF-1 complex exerted a positive effect on learning ability and the retention of long-term spatial memory in 6-month-old male 5xFAD mice. Four-week treatment with Roxadustat significantly reduced pathological morphological alterations in cells of the prefrontal cortex. In addition, animals treated with Roxadustat exhibited significantly increased expression of the brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Our findings suggest that stabilization of the HIF-1 complex through inhibition of HIF prolyl hydroxylase may represent a promising strategy for neuroprotection in AD. Full article

This paper examines how technological innovation in next-generation probiotics shapes consumer trust through the lens of perceived safety. Rapid advances—spanning conventional cultures (Tier 1), postbiotics (Tier 2), and engineered microbial strains (Tier 3)—are transforming functional food architectures, yet consumer trust remains a critical determinant of their successful development, application, and adoption. Drawing on interdisciplinary evidence from food microbiology, consumer perception research, and regulatory analysis, this study examines and evaluates how these distinct technological innovation tiers alter public risk dynamics. Findings indicate that processing methodologies, media framing, and the spread of misinformation significantly influence public perceptions of microbial legitimacy, while the “Animation Gap” and “Contamination Anxiety” introduce qualitatively new cognitive friction points. Furthermore, regulatory inconsistencies across jurisdictions and variability in health claim substantiation further complicate market uptake. Streamlined case-based evidence highlights physical stability, sensory performance, and explicit value metrics that determine whether technological innovations are trusted or rejected by consumers. The paper argues that bridging the gap between scientific innovation and public acceptance requires proactive communication strategies, ethical marketing practices, and participatory engagement strategies grounded in empirical integrity. In addition, digital ecosystems, including social media and algorithm-driven content exposure, play an increasingly influential role in amplifying technology neophobia, underscoring the need for robust, targeted, evidence-based public communication in the evolving landscape of probiotic and functional food innovation. Full article

Animal Crossing is a famous cozy video game in which players embody a human character living among anthropomorphic animals. Playing Animal Crossing has been evidenced to fulfill players’ Maslow’s needs, such as deficiency-motivated needs (safety, love and esteem—with the exception of physical needs) and growth-motivated needs (cognitive, esthetic, and self-actualization needs). We can suggest that animal characters, with their cute esthetic, are an important part of the game’s success. If such a virtual society is a safe place for humans (players and characters), what messages does it convey regarding our interactions with nature and other species? To answer this question, we investigated the relationships between players and nonhuman species in Animal Crossing: New Horizons and Animal Crossing: Pocket Camp Complete. Positive effects of such interspecies interactions have been observed at both intra- and extradiegetic levels: an improved knowledge of the animal kingdom and an improved sensitivity to its diversity. However, the game also has negative sides: its speciesist, colonialist and capitalist dynamics promote animals’ objectification. We then discuss how players can transform the game to consider all animal species with equal respect, and how other games with more ethical dynamics are a good model for further game designs. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, neuroinflammation, mitochondrial dysfunction, and oxidative stress. Despite recent advances, current therapies offer little benefit, and AD remains a significant challenge. Polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have attracted attention for their neuroprotective effects primarily through anti-inflammatory and antioxidant properties, but also for their ability to influence membrane fluidity and neuronal function. DHA is the predominant omega-3 PUFA in nerve cell membranes and is critical for synaptic plasticity and cognitive function. Some evidence has demonstrated that marine omega-3 supplementation reduces Aβ deposition, modulates microglial activation, and prevents cognitive decline in animal models. Even with heterogeneous results, preclinical and clinical studies suggest that long-term DHA/EPA supplementation can improve cognitive function in subjects with mild cognitive impairment (MCI) and reduce neuroinflammation markers. However, individual variability and brain bioavailability pose significant challenges. This review summarizes and discusses the current knowledge on the importance of PUFAs for human health, exploring novel mechanistic hypotheses, such as the effect of omega-3 fatty acids on brain iron homeostasis, the microbiota–gut–brain axis, the glymphatic system, and miRNAs. Furthermore, it focuses on the therapeutic potential of PUFAs in the treatment of AD and proposes future directions for translational research. Full article

Background/Objectives: Chronic stress contributes to anxiety disorders and cognitive impairment, while effective multi-target therapeutic strategies remain limited. This study investigated the effects of a standardized extract prepared from the aerial parts of Bacopa monnieri (L.) Wettst. (Brahmi) extract and an anthocyanin-rich mixed Thai berry extract, administered individually and in combination, in a chronic unpredictable mild stress (CUMS) rat model. Methods: Extracts derived from Morus alba L. (mulberry), Antidesma ghaesembilla Gaertn. (mamao), and Syzygium nervosum DC. (ma-kiang) were characterized for anthocyanin and phenolic contents, antioxidant activities, and cyanidin-3-O-glucoside levels using HPLC. Male Sprague Dawley rats were subjected to a 14-day CUMS protocol and treated with Brahmi extract, mixed Thai berry extract, or their combinations. Behavioral assessments included the open-field test, elevated plus maze, and novel object recognition test. Histopathological evaluation of the prefrontal cortex and hippocampus was also performed. Results: Brahmi extract and mixed Thai berry extract attenuated selected anxiety-related behaviors and improved recognition memory-related parameters in CUMS-exposed rats. The low-dose berry extract produced the most consistent behavioral improvements, whereas combination-treated groups showed greater histological preservation. Histopathological analysis revealed reduced neuronal degeneration and improved tissue organization in the prefrontal cortex and hippocampus of treated animals. Conclusions: These findings support the potential therapeutic relevance of Bacopa monnieri and anthocyanin-rich Thai berry extracts under chronic stress conditions, with differential effects observed between individual and combination treatments. Full article

Consumption trends have shifted towards added-value, natural, less-processed, and more nutritious foods. Key factors shaping these trends include animal welfare, sustainability, globalization, cultural influences, socio-demographics, food safety, health, and nutrition. This structured and narrative review, following a systematic approach, analyzes future trends in food consumption, considers preclinical and clinical studies, and examines related industrial challenges. A comprehensive search across Scopus, Web of Science, and Google Scholar was conducted, including original articles and reviews on food consumption trends or industrial processes, using Boolean operators. Potential gaps and biases of the analyzed articles were also included. Of 8742 articles, 58 studies were included. It was found that animal welfare has led consumers to adopt plant-based alternatives, protein, and more sustainable food consumption. Rising health awareness has led to the development of personalized nutrition, functional, and nanoparticle-encapsulated nutrient-based foods. Physiologically, trends indicate improvements in body weight, glycemic control, and lipid profiles, whereas emerging formulations show promise in enhancing cognitive function and nutrient bioavailability. Industrial challenges include refining and scaling up new technologies, encouraging sustainable production practices, ensuring food safety, fulfilling consumer demands, and developing safe, nutritious, and functional foods. Compliance with global health regulations should be prioritized. Continued multidisciplinary research is essential to understand the impact of emerging food trends on consumer health. Full article

Background/Objectives: Emotion recognition is a fundamental component of mammalian social cognition, enabling animals such as rodents to detect the emotional states of conspecifics and guide prosocial or avoidance behaviors. However, natural social landscapes are highly complex and multi-targeted. Furthermore, it remains unknown how an observer’s own internal emotional state dictates social target prioritization in these dynamic environments. Methods: We used a novel multi-target social paradigm wherein observer mice subjected to naïve, positive (relieved), or negative (acute stress) experiences, interacting simultaneously with demonstrator mice in neutral, relieved, or stressed states. We utilized in vivo fiber photometry to record anterior cingulate cortex (ACC) calcium dynamics during these complex interactions, and employed bidirectional optogenetics to establish causal neural mechanisms. Results: Naïve and relieved observer mice exhibited a rapid, innate behavioral prioritization of acutely stressed conspecifics. Conversely, an internal state of acute stress experience in the observer completely abolished this early-stage discrimination. Fiber photometry revealed that ACC excitatory neuronal activity robustly encodes the prioritization of stressed conspecifics, a neural signature that is fundamentally suppressed in stressed observers. Optogenetic inhibition of the ACC abolished innate social preference in naïve and relieved mice, whereas targeted ACC activation successfully overrode internal stress to restore social discrimination in stressed observers. Conclusions: Acute negative internal states profoundly suppress social discrimination ability. The ACC acts as a state-dependent gatekeeper to dictate social prioritization. Full article

α-Synuclein (α-Syn) is a key presynaptic protein, primarily known for its role in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies, including dementia with Lewy bodies (DLB). Although much of the research has focused on the nigrostriatal dopamine (DA) pathway, there is growing recognition that the accumulation of misfolded α-Syn in the prefrontal cortex (PFC) is a critical driver of non-motor symptoms and cognitive deficits in PD and DLB. This review examines the dual role of α-Syn in the PFC circuitry, initially exploring its regulation of synaptic vesicle (SV) dynamics and recycling to maintain stable neurotransmission. We highlight its contribution to the modulation of glutamatergic (Glu) and GABAergic (γ-aminobutyric acid, GABA) synapses, which ensures the functional excitatory/inhibitory (E/I) balance of prefrontal circuits. Conversely, in PD and DLB, the transition of functional α-Syn monomers to pathological oligomers triggers a cascade of synaptic failures. We analyze how α-Syn aggregation causes pathology in dendritic spines, leads to a progressive reduction in the density of synaptic markers, and impairs cortical plasticity. Synthesizing evidence from neuroimaging studies, post-mortem human cortical samples, and animal models, this review emphasizes the PFC as a vulnerable brain region where α-Syn-mediated synaptic dysfunction translates into cognitive and emotional deficits. Deciphering these early synaptic alterations is essential for developing neuroprotective strategies that preserve cortical function in PD and DLB. Full article

We developed a laboratory-based setup to perform behavioral tests of the effect of the neonicotinoid insecticide Thiacloprid in the CALYPSO^® formulation on bumblebees. This setup simulates essential components of navigation and pollination under natural conditions. The behavioral components are exploration, exploratory learning, learning of a rewarded local cue in the context of a specific panorama, and retrieving the memory for this association. The walking bumblebees navigated under their own motivation between a fully functional colony and a training/test arena. They explored the arena and learned the association of a rewarded local cue in the context of a panorama. The rule of association was that the local cue was bound to a particular part of the panorama irrespective of where it appeared in its spatial relation to the entrance gate through which the animal came from the colony. Extinction tests were performed for two conditions, match and mismatch. The match condition resembled the training condition. In the mismatch condition the local cue appeared in a different part of the panorama. Solving this task requires the learning and remembering of a rule under variable conditions, mimicking the cognitive requirements faced by bumblebees under natural conditions. The control animals solved this task, whereas animals treated with Thiacloprid 400 ng CALYPSO^® diluted in 4 µL per animal were significantly compromised, as shown by several parameters of the walking trajectories under the match and mismatch conditions. No dose–response functions were established, but a volume of 800 ng CALYPSO^® diluted in 8 µL per animal did not show any significant differences from a volume of 4 µL CALYPSO^®. The setup and the experimental paradigm are suitable for routine quantitative tests on the effects of insecticides on the cognitive faculties of insects during navigation and pollination. Full article

Temporal lobe epilepsy (TLE) is a common drug-resistant epilepsy characterized by recurrent seizures, cognitive impairment, aberrant adult hippocampal neurogenesis, inhibitory circuit disruption, and persistent inflammatory remodeling. Current anti-seizure medications primarily offer symptomatic control and do not target the progressive structural and functional deterioration of epileptic hippocampal networks. Here, we investigated whether local nerve growth factor (NGF)-hydrogel delivery during the latent phase after status epilepticus could mitigate hippocampal pathological remodeling and improve long-term outcomes in a kainic acid (KA)-induced mouse model (utilizing C57BL/6J and Nestin-CreERT2 mice). Animals were randomly assigned to three groups: the saline control group, the untreated KA epilepsy group, and the KA + NGF-hydrogel treatment group. NGF-hydrogel was administered into hippocampal Cornu Ammonis 1 (CA1) beginning 3 days post-kainic acid and repeated every 15 days. Histological, immunofluorescence, circuit-tracing, electrophysiology, electroencephalography (EEG), and behavioral assessments were used to evaluate neurogenesis, microenvironment, circuit readouts, seizure burden, and cognition. NGF-hydrogel treatment was associated with preserved dentate gyrus neural stem cell populations, improved newborn granule cell localization and maturation, attenuated neuroinflammation and gliosis, and partial recovery of inhibitory interneuron markers. These changes were accompanied by improved hippocampal circuit readouts, reduced chronic spontaneous seizure burden, and enhanced recognition and spatial memory. Our findings indicate that local NGF-hydrogel delivery following status epilepticus is associated with improved hippocampal remodeling and functional outcomes, and suggest that biomaterial-based neurotrophic support may be a promising strategy for providing targeted neuroprotection and facilitating excitatory/inhibitory (E/I) balance reconstruction in the epileptic hippocampus. Full article

Immovable cultural heritage, including archaeological sites, historic buildings, and long-standing landscape structures, is typically interpreted through historical, aesthetic, and identity-based perspectives. This paper proposes an alternative reading, situating heritage within the broader context of coupled environmental, biological, and human systems. Grounded in non-equilibrium thermodynamics and system ecology, the study advances an ecophysical perspective in which heritage is understood as a persistent structural and informational component of the human niche. Drawing on evidence from building physics, landscape ecology, environmental psychology, and health-related research, this paper discusses the scientific plausibility of heritage-mediated effects, including environmental buffering, habitat stabilization, and cognitive and physiological regulation. These heterogeneous processes are reinterpreted within a unified conceptual framework, HEROS (HERitage One Health System), which links observable indicators to underlying mechanisms of organization and dissipation. A simplified stock–flow formulation, consistent with ecophysics and system ecology literature, is introduced to illustrate how heritage may influence dissipation across environmental, animal, and human subsystems. Rather than presenting a fully operational model, this perspective aims to reposition heritage within One Health and sustainability frameworks, highlighting its potential role in supporting system stability, resilience, and long-term continuity. Full article

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by complex interactions among genetic, environmental, and biological factors. Increasing evidence suggests that immune system processes intersect with neurodevelopment in ways that may influence brain maturation, synaptic organization, and large-scale network function. However, existing literature is often fragmented across molecular, cellular, and systems levels, limiting the development of a coherent interpretive framework. In this review, we propose a developmental neuroimmune cascade model of ASD, in which early-life immune perturbations, arising from prenatal or perinatal factors, may interact with genetic susceptibility to influence cytokine signaling, microglial function, blood-brain barrier dynamics, and gut-immune communication. These processes may, in turn, affect synaptic pruning, excitatory-inhibitory balance, and the maturation of neural circuits, contributing to alterations in large-scale brain networks implicated in sensory processing, interoception, and social cognition. We synthesize evidence from observational human studies, postmortem analyses, and experimental animal models to examine how immune-related mechanisms may contribute to neurodevelopmental trajectories associated with ASD, while explicitly distinguishing associative findings from mechanistic inference. Particular attention is given to the role of distributed network vulnerability, including, but not limited to, insula-centered systems that integrate internal bodily states with affective and cognitive processing. Finally, we consider implications for biomarker development and stratified intervention approaches, emphasizing the importance of developmental timing, biological heterogeneity, and cautious interpretation of translational potential. Rather than positioning immune dysfunction as a singular cause of ASD, this model conceptualizes neuroimmune processes as modulators of developmental trajectories, offering a structured basis for future research linking immune signaling to circuit-level and behavioral outcomes. Full article

Alzheimer’s disease (AD), the leading cause of dementia, is characterized by progressive cognitive decline along with hallmark brain pathologies including amyloid-beta accumulation, hyperphosphorylated tau, neuroinflammation and neuronal mitochondrial dysfunction. As current pharmaceutical treatments only provide modest symptomatic improvement, there is an urgent need for effective non-pharmaceutical treatment options for the prevention or slowing down of this disease. This review synthesizes results from randomized controlled trials, observational studies, and animal model research on the ability of exercise to influence cognitive functions, brain structural changes, inflammatory processes, and neuroplasticity-related pathways. Exercise has demonstrated the capacity to enhance neurotrophic signaling, improve the regulation of mitochondria, improve cerebrovascular function and reduce pro-inflammatory cytokine levels in preclinical and mild cognitive impairment (MCI) subjects. Additionally, aerobic and resistance training has been shown to enhance physical performance and functional capacity. Furthermore, mind–body, dual-task and multimodal types of interventions may also provide additional cognitive and psychological benefits. Although the overall cognitive effect of exercise in individuals with established AD is generally small, it has been demonstrated that exercise can contribute to maintaining brain health through multiple interconnected metabolic, vascular and molecular pathways, thereby preserving cognitive reserve and slowing disease progression, particularly when initiated during early to midlife prior to the onset of AD symptoms. Therefore, future research will require establishing stage-specific exercise recommendations based on modality type, intensity and duration to achieve optimal clinical outcomes. Full article

Background: Heavy metals and per- and polyfluoroalkyl substances (PFAS) are widespread environmental pollutants that have been linked to worsening cognition, but how the two classes act together to shape cognitive function is still not well characterized. Drawing on data from the National Health and Nutrition Examination Survey (NHANES), this observational analysis evaluated how PFAS and metals are jointly related to performance across distinct cognitive domains in older adults. Methods: We analyzed 1447 adults aged 60 years and older from the 2011–2012 NHANES cycle in a cross-sectional design study. Metal levels in serum and whole blood were determined with standardized laboratory assays. Associations of single exposures and of the overall mixture with the CERAD word-learning and recall tasks, Animal Fluency, and the Digit Symbol Substitution Test were assessed using multivariable linear regression, together with Bayesian Kernel Machine Regression (BKMR). Results: Single-exposure models produced largely modest and inconsistent associations across the cognitive measures. Within the mixture models, PFAS, especially PFOA, PFDE, and PFOS, were repeatedly flagged as influential across several domains, whereas the metals tended to matter for specific outcomes only. The strongest negative signals at elevated joint exposure emerged for memory-related measures, notably CERAD Trials 1 and 2. Conclusions: Joint exposure to PFAS and heavy metals appears to influence cognitive domains unevenly, with memory-related measures seeming more responsive as combined exposure rises. These results reinforce the value of mixture-oriented analytic strategies when investigating environmental contaminants in relation to cognitive aging. Full article

Background/Objectives: Excitotoxicity, primarily caused by excessive glutamate signaling, is a significant contributor to the aetiology of several neurological disorders. Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, is known for its neuroprotective properties, including antioxidants and anti-inflammatory effects. However, the existing literature has not sufficiently reviewed its specific role in glutamate-induced excitotoxicity. This systematic review aimed to provide comprehensive information from the literature on the neuroprotective effects of DHA in models of glutamate-induced neurotoxicity. Methods: A systematic search was conducted in the Cochrane Library, Scopus, Web of Science, PubMed, ScienceDirect, and Google Scholar, following PRISMA 2020 guidelines. The following keywords were used: DHA OR docosahexaenoic acid AND excitotoxicity OR glutamate-induced excitotoxicity OR glutamate-induced neurotoxicity. A total of 475 articles were screened, and 13 original articles published between 2003 and 2025 were included for data extraction. These studies included nine in vivo animal studies, three ex vivo studies, and one in vitro study. The risk of bias was assessed using SYRCLE’s methodology. Results: Our findings demonstrate that DHA provides substantial neuroprotection against excitotoxicity through antioxidative, anti-inflammatory, and anti-apoptotic mechanisms. Furthermore, DHA enhances neuronal function and cognitive performance by modulating neurotransmitter levels and glutamate-related signaling pathways. Despite these positive outcomes, heterogeneity across studies suggests that the neuroprotective properties of DHA may be affected by various parameters, such as the source of DHA, treatment dose and duration, age and experimental design. Conclusions: Although previous studies have demonstrated the benefits of DHA in preclinical and clinical settings of neurological disorders, further clinical studies focusing on the modulation of excitotoxicity by DHA are needed to validate its translational efficacy and therapeutic significance. Full article