Search Results (52)

Astrocytes play a crucial role in maintaining neuronal microenvironment homeostasis and regulating synaptic plasticity within the hippocampus. Magnoflorine (MGN), a naturally occurring isoquinoline alkaloid, has demonstrated biological activity in the central nervous system. However, its effects on astroglial cells remain poorly understood. The present study aimed to evaluate the impact of acute and chronic administration of MGN (10 and 20 mg/kg body weight) on the morphology and morphometric parameters of GFAP-positive astrocytes in the CA1 field of the mouse hippocampus. Immunohistochemical and morphometric analyses were performed in the oriens layer (SO), pyramidal layer (SP), radiate layer (SR), and lacunose-molecular layer (SLM). MGN significantly modulated astrocyte density, cell size, and the number of processes in a dose-, time-, and layer-dependent manner. A heterogeneous and layer-specific astroglial response was particularly evident following chronic administration of the tested compound. Together with the observed lack of significant differences in analysed parameters, decreases were mainly detected after administration of the low MGN dose, whereas the 20 mg/kg dose induced primarily increased structural complexity. Thus, the direction of changes was not uniform across all layers. The most prominent changes were detected in the SLM layer. Overall, MGN modulated astrocyte morphology and reactivity in a context-dependent manner. These findings indicate a modulatory influence of MGN on astroglial structural plasticity rather than a uniform directional effect. Although the observed changes may be associated with alterations in astroglia-mediated mechanisms involved in maintaining neuronal homeostasis and responses to stress, their functional significance requires further investigation. Full article

The brain has a higher energy demand per unit weight than any other organ in the body; however, links between metabolism, diet and neurological function have historically been underexplored. This partly stems from early assumptions that brain metabolism is primarily dependent on glucose and ketone bodies, whereas more recent evidence indicates broader metabolic flexibility and complex cell-type specialisation. In the past few decades, brain metabolism has become increasingly recognised as relevant to neurological and mental health, and many neurodegenerative disorders are accompanied by changes in brain energy utilisation. In parallel, epidemiological studies associate hypercaloric dietary patterns and metabolic disorders—particularly type-2 diabetes mellitus—with increased risk of later cognitive decline and sporadic Alzheimer’s disease, although causal pathways remain difficult to establish in humans. In this narrative review, we summarise selected findings linking “unhealthy” diets to synaptic function, focusing on synaptic plasticity, neuroinflammation and adult hippocampal neurogenesis, and we distinguish between evidence from human observational studies and mechanistic insights from animal and cellular models. We also discuss candidate mechanisms—including insulin resistance-linked signalling changes, lipid-driven inflammatory amplification, oxidative stress, and altered lipid handling—that may contribute to synaptic vulnerability. Finally, we outline translational considerations and key knowledge gaps (including physiological exposure levels and heterogeneity of experimental paradigms) that currently limit inference from preclinical models to clinical intervention. Full article

This paper proposes a high-precision theoretical and computational neurorehabilitation framework for Mild Cognitive Impairment (MCI), connecting computational neuroscience and clinical practice through qEEG-guided neurofeedback training (NFT). By employing sLORETA to identify putative pathological nodes within the Default Mode Network (DMN)—specifically the Precuneus and the Posterior Cingulate—the model utilizes spectral decomposition to isolate the aperiodic 1/f component, reducing background noise bias and allowing the calculation of a pure individual alpha frequency (IAF) to inform recalibration of Weber’s Cognitive Threshold. The core architecture uses Bayesian algorithms and stochastic modeling to drive a Dynamic Weight Change mechanism. To support Long-Term Potentiation (LTP) and Hebbian learning, reward thresholds are modulated in real time to target a 70% success rate, as a strategic rationale to anticipate neural fatigue while maintaining the Reward Prediction Error required for synaptic strengthening. As a prospective validation pathway, future studies may assess clinical value through changes in MoCA and RAVLT scores, as well as by examining normalization of cortical coherence in the Default Mode Network (DMN). By merging computational neuroscience with biological models of synaptic plasticity, this work outlines how individual biology can be mapped into an explicit mathematical model. The proposed framework may inform an individualized protocol that provides an objective model-based measure of cognitive recovery, suggesting a replicable and robust strategy for neurorehabilitation during the prodromal phase of dementia, and providing a new approach to neuroscience-based cognitive rehabilitation. This work is intended as a theoretical and computational framework; no complete empirical dataset is reported in the present manuscript. Full article

Aging is characterized by progressive degeneration of neuromuscular junctions (NMJs), which significantly contributes to muscle weakness and the development of sarcopenia. Photobiomodulation (PBM), a non-invasive therapeutic method based on the use of low-intensity light, has shown promising results in mitigating muscle degeneration in both experimental and clinical studies. The aim of this study was to evaluate the ultrastructural effects of photobiomodulation on neuromuscular junctions and skeletal muscle fibers in the m. vastus lateralis muscle of aged rats using light and transmission electron microscopy. Male Wistar rats (18 months old, body weight 650–800 g, n = 10) were subjected to photobiomodulation of the right m. vastus lateralis muscle (650 nm, 6 J/cm², four consecutive daily sessions of 3 min each). The contralateral left limb served as an untreated control. Muscle samples were analyzed by light and transmission electron microscopy. Histological examination revealed typical age-related changes in control muscles, including variability in muscle fiber diameter, centrally located nuclei, and an increased volume of connective tissue. Ultrastructural analysis confirmed signs of skeletal muscle aging, such as myofibril fragmentation, sarcomere disorganization, lipofuscin accumulation, and tubular aggregate formation. Morphometric analysis of neuromuscular junctions after photobiomodulation showed an increase in the number of active zones on the presynaptic membrane, elongation of the postsynaptic membrane, and a reduction in the width of the synaptic cleft. In addition, mitochondrial hyperplasia was observed in presynaptic terminals, while the total number of synaptic vesicles decreased. These findings indicate a compensatory reorganization of neuromuscular junctions and suggest that photobiomodulation can enhance their functional activity in aged skeletal muscle. Full article

Eating behavior requires a balance between metabolic and hedonic components. Anxiety and dietary type may influence the quantity, patterns, and other aspects of food intake. Modern diets, especially in Western societies, often contain high levels of calories from fat and simple sugars (e.g., cafeteria-style diets). This type of diet may promote overweight and/or obesity in some, although many consumers remain at a normal weight. The mechanisms underlying susceptibility or resistance to weight gain remain unclear. Here, Sprague-Dawley male rats were fed a cafeteria diet for 10 weeks and then classified into quartiles based on body mass. We evaluated locomotor activity and anxiety-like behaviors and analyzed hypothalamic proteomics in overweight (Q4) rats compared with underweight (Q1) rats. Our results showed that locomotor activity and anxiety-like behaviors did not differ across quartiles (p > 0.05). Nevertheless, the expression of several hypothalamic proteins differed between Q4 and Q1 rats. Functional enrichment analysis of these differentially expressed proteins (p ≤ 0.05) revealed changes in cytoskeleton dynamics, synaptic communication, energy production and utilization, biosynthesis of cellular components (including nucleotides and carbohydrates), and regulation of metabolism between Q1 and Q4 rats. Neuro-humoral hypothalamic output regulates metabolism and food intake. Therefore, these functional changes in the hypothalamus may be associated with rats’ susceptibility/resistance to weight gain. Full article

Cholinergic dysfunction and impaired synaptic plasticity are key mechanisms underlying cognitive decline in neurodegenerative conditions, including Alzheimer’s disease (AD). Schisandra chinensis pomace (SSP), a by-product of fruit processing, contains bioactive lignans and polyphenols with reported neuroprotective properties; however, its effects under cholinergic dysfunction have not been systematically investigated. In this study, the effects of SSP on scopolamine-induced cognitive impairment were evaluated using ex vivo electrophysiological and in vivo behavioral approaches. Multi-electrode array recordings demonstrated that SSP at 0.1 mg/mL significantly restored scopolamine-suppressed hippocampal long-term potentiation (LTP), whereas a higher concentration (1.0 mg/mL) did not restore hippocampal synaptic potentiation. In vivo, C57BL/6N mice received oral SSP (50 or 100 mg/kg/day) for six weeks, with scopolamine administered during the final three weeks. SSP at 50 mg/kg prevented scopolamine-induced body weight loss, attenuated hyperlocomotor activity, and significantly improved memory retention, as evidenced by enhanced performance in the passive avoidance and Morris water maze tests. Furthermore, SSP restored hippocampal brain-derived neurotrophic factor (BDNF) expression and reduced the p-JNK/JNK ratio, indicating modulation of neurotrophic and stress-responsive signaling pathways. Collectively, these findings suggest that SSP attenuates scopolamine-induced cholinergic dysfunction, accompanied by improved hippocampal synaptic plasticity and changes in BDNF and JNK signaling. These results support the potential of SSP as a neuroactive botanical resource under cholinergic challenge. Full article

Obesity is an epidemic that currently impacts many nations. The persistence of this disease is shaped by both genetic and epigenetic factors that extend beyond calorie balance. Research in the past year has revealed that epigenetic and cellular memory within adipose tissue can predispose individuals to weight regain after initial fat loss, as shown by studies indicating persistent transcriptional and chromatin changes even after fat mass reduction. Independent studies also demonstrate long-lasting metabolic shifts, such as those triggered by glucose-dependent insulinotropic polypeptide receptor (GIPR)-induced thermogenesis and sarcolipin (SLN) stabilization that also support a form of “metabolic memory” that is associated with sustained weight loss. At the neural level, rare variants in synaptic genes like BSN (Bassoon presynaptic cytomatrix protein), a presynaptic scaffold protein, and APBA1 (amyloid beta precursor protein binding family A member 1), a neuronal adaptor involved in vesicular trafficking, disrupt communication in feeding circuits, elevating obesity risk and illustrating how synaptic integrity influences food intake regulation. Similarly, the spatial compartmentalization of metabolic signaling within neuronal cilia is emerging as crucial, with cilia-localized receptors G protein-coupled receptor 75 (GPR75) and G protein-coupled receptor 45 (GPR45) exerting opposing effects on energy balance and satiety. Meanwhile, genome-wide association studies (GWAS) have advanced through larger, more diverse cohorts and better integration of environmental and biological data. These studies have identified novel obesity-related loci and demonstrated the value of polygenic risk scores (PRS) in predicting treatment responses. For example, genetic variants in GLP-1R (glucagon-like peptide-1 receptor) and GIPR (glucose-dependent insulinotropic polypeptide receptor) may modulate the effectiveness of incretin-based therapies, while PRS for satiation can help match individuals to the most appropriate anti-obesity medications. This review focuses on studies in the last two years that highlight how advances in obesity genetics are driving a shift toward more personalized and mechanism-based treatment strategies. Full article

Muscle wasting and weakness are critical clinical problems that limit mobility and independence, reduce health span, and increase the risk of physical disability. The molecular basis for this has not been fully determined. Klotho expression is downregulated in conditions associated with muscle wasting, including aging, chronic kidney disease, and myopathy. The objective of this study was to investigate a mechanistic role for Klotho in regulating muscle wasting and weakness. Body weight, lean mass, muscle mass, and myofiber caliber were reduced in Klotho-deficient mice. In the tibialis anterior muscle of Klotho-null mice, type IIa myofibers were resistant to changes in size, and muscle composition differed with a higher concentration of type IIb fibers to the detriment of type IIx fibers. Glycolytic GPDH enzymatic activity also increased. Klotho-deficient mice showed impaired muscle contractility, with reduced twitch force, torque, and contraction–relaxation rates. RNA sequencing revealed upregulation of synaptic and fetal sarcomeric genes, prompting us to examine muscle innervation. Klotho deficiency led to neuromuscular junction remodeling, myofiber denervation, and functional motor unit loss. Loss of motor units correlated with absolute torque. Collectively, these findings reveal a novel mechanism through which systemic Klotho deficiency disrupts muscle synapses and motor unit connectivity, potentially contributing to muscle wasting and weakness. Full article

Despite its significance, hysteresis remains underrepresented in mainstream models of plasticity. In this work, we propose a novel framework that explicitly models hysteresis in simple one- and two-neuron models. Our models capture key feedback-dependent phenomena such as bistability, multistability, periodicity, quasi-periodicity, and chaos, offering a more accurate and general representation of neural adaptation. This opens the door to new insights in computational neuroscience and neuromorphic system design. Synaptic weights change in several contexts or mechanisms including, Bienenstock–Cooper–Munro (BCM) synaptic modification, where synaptic changes depend on the level of post-synaptic activity; homeostatic plasticity, where all of a neuron synapses simultaneously scale up or down to maintain stability; metaplasticity, or plasticity of plasticity; neuromodulation, where neurotransmitters influence synaptic weights; developmental processes, where synaptic connections are actively formed, pruned and refined; disease or injury; for example, neurological conditions can induce maladaptive synaptic changes; spike-time dependent plasticity (STDP), where changes depend on the precise timing of pre- and postsynaptic spikes; and structural plasticity, where changes in dendritic spines and axonal boutons can alter synaptic strength. The ability of synapses and neurons to change in response to activity is fundamental to learning, memory formation, and cognitive adaptation. This paper presents simple continuous and discrete neuro-modules with adapting feedback synapses which in turn are subject to feedback. The dynamics of continuous periodically driven Hopfield neural networks with adapting synapses have been investigated since the 1990s in terms of periodicity and chaotic behaviors. For the first time, one- and two-neuron models are considered as parameters are varied using a feedback mechanism which more accurately represents real-world simulation, as explained earlier. It is shown that these models are history dependent. A simple discrete two-neuron model with adapting feedback synapses is analyzed in terms of stability and bifurcation diagrams are plotted as parameters are increased and decreased. This work has the potential to improve learning algorithms, increase understanding of neural memory formation, and inform neuromorphic engineering research. Full article

Ensuring efficient long-term quality control of the raw mix remains a priority for the cement industry, supporting initiatives to lower the CO₂ footprint by incorporating significant amounts of alternative fuels and raw materials in clinker production. This study presents an effective method for creating a robust auto-tuner for proportional–integral–differential (PID) controller control of the lime saturation factor (LSF) of the raw mix using artificial neural networks (ANNs). This auto-tuner, combined with a previously studied robust PID controller, forms an integrated system that adapts to process changes and maintains low long-term variance in LSF. The ANN links each of the three PID gains to the process dynamic parameters, with the three ANNs also interconnected. We employed the Levenberg–Marquardt method to optimize the ANNs’ synaptic weights and applied the weight decay method to prevent overfitting. The industrial implementation of our control system, using the auto-tuner for 16,800 h of raw mill operation, shows an average LSF standard deviation of 2.5, with fewer than 10% of the datasets exceeding a standard deviation of 3.5. Considering that the measurement reproducibility is 1.44 and assuming a low mixing ratio of the raw meal in the silo equal to 2, the LSF standard deviation in the kiln feed approaches the analysis reproducibility, indicating that disturbances in the raw meal largely diminish in the kiln feed. In conclusion, integrating traditional, well-established tools like PID controllers with newer advanced techniques, such as ANNs, can yield innovative solutions. Full article

Chimera states and bump states are collective synchronization phenomena observed independently (in different parameter regions) in networks of coupled nonlinear oscillators. And while chimera states are characterized by coexistence of coherent and incoherent domains, bump states consist of alternating active and inactive domains. The idea of multistable plasticity in the network connections originates from brain dynamics where the strength of the synapses (axons) connecting the network nodes (neurons) may change dynamically in time; when reaching the steady state the network connections may be found in one of many possible values depending on various factors, such as local connectivity, influence of neighboring cells etc. The sign of the link weights is also a significant factor in the network dynamics: positive weights are characterized as excitatory connections and negative ones as inhibitory. In the present study we consider the simplest case of bistable plasticity, where the link dynamics has only two fixed points. During the system/network integration, the link weights change and as a consequence the network organizes in excitatory or inhibitory domains characterized by different synaptic strengths. We specifically explore the influence of bistable plasticity on collective synchronization states and we numerically demonstrate that the dynamics of the linking may, under special conditions, give rise to co-existence of bump-like and chimera-like states simultaneously in the network. In the case of bump and chimera co-existence, confinement effects appear: the different domains stay localized and do not travel around the network. Memory effects are also reported in the sense that the final spatial arrangement of the coupling strengths reflects some of the local properties of the initial link distribution. For the quantification of the system’s spatial and temporal features, the global and local entropy functions are employed as measures of the network organization, while the average firing rates account for the network evolution and dynamics. In particular, the spatial minima of the local entropy designate the transition points between domains of different synaptic weights in the hybrid states, while the number of minima corresponds to the number of different domains. In addition, the entropy deviations signify the presence of chimera-like or bump-like states in the network. Full article

The brain is a biological system comprising nerve cells and orchestrates its embodied agent’s perception, behavior, and learning in dynamic environments. The free-energy principle (FEP) advocated by Karl Friston explicates the local, recurrent, and self-supervised cognitive dynamics of the brain’s higher-order functions. In this study, we continue to refine the FEP through a physics-guided formulation; specifically, we apply our theory to synaptic learning by considering it an inference problem under the FEP and derive the governing equations, called Bayesian mechanics. Our study uncovers how the brain infers weight changes and postsynaptic activity, conditioned on the presynaptic input, by deploying generative models of the likelihood and prior belief. Consequently, we exemplify the synaptic efficacy in the brain with a simple model; in particular, we illustrate that the brain organizes an optimal trajectory in neural phase space during synaptic learning in continuous time, which variationally minimizes synaptic surprisal. Full article

Krill oil (KO) has been described as having the potential to ameliorate the detrimental consequences of a high-fat diet (HFD) on the aging brain, though the magnitude and mechanism of this benefit is unclear. We thus hypothesized that dietary KO supplementation could counteract the effects of cognitive aging and an HFD on spatial learning, neuroinflammation, neurogenesis, and synaptic density in the cortex and hippocampus of aged rats. Sixteen-month-old Sprague Dawley rats were fed for 12 weeks while being divided into four groups: control (CON); control with KO supplementation (CONKO); high-fat diet (HF); and high-fat diet with KO supplementation (HFKO). We measured food consumption, body mass, spatial memory (Morris water maze), microglia, neurogenesis, cytokine concentrations, and synaptic markers (post-synaptic density-95 and synaptophysin). Predictably, an HFD did induce significant differences in body weights, with the high-fat groups gaining more weight than the low-fat controls. However, KO supplementation did not produce significant changes in the other quantified parameters. Our results demonstrate that the dietary KO dose provided in the current study does not benefit hippocampal or cortical functions in an aging model. Our results provide a benchmark for future dosing protocols that may eventually prove to be beneficial. Full article

The vagus nerve regulates metabolic homeostasis and mediates gut–brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut–brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut–brain axis. Targeting the gut–brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke. Full article

The title compound, unimer U (tpy stands for 2,2′:6′,2″-terpyridin-4′-yl end-group), by itself shows the memristor effect with a retention time of 18 h and persistence of 11 h. Its coordination copolymer with Co(II) ions, [CoU]_n, exhibits multimodal resistance changes similar to the synaptic responses observed in biological systems. More than 320 cycles of potentiation and depression measured in continuous sequence occurred without observing a significant current change, confirming the operational stability and reproducibility of the device based on the [CoU]_n polymer. The synaptic effect of a device with an indium tin oxide (ITO)/[CoU]_n/top-electrode (TE) configuration is more pronounced for the device with TE = Au compared to devices with TE = Al or Ga. However, the latter TEs provide a cost-effective approach without any significant compromise in device plasticity. The detected changes in the synaptic weight, about 12% for pair-pulse facilitation and 80% for its depression, together with a millisecond trigger and reading pulses that decay exponentially on the time scale typical of neurosynapses, justify the device’s ability to learn and memorize. These properties offer potential applications in neuromorphic computation and brain-inspired synaptic devices. Full article