Search Results (6,047)

In multiple system atrophy (MSA), the fatal movement disorder, cell populations of the striatum and other subcortical brain regions degenerate, leading to a rapidly progressive, atypical Parkinsonian syndrome. The pathophysiology of neurons and glial cells shows misfolding, aggregation, and increased release of the protein α-synuclein. In addition, neuronal hypoexcitability, a reduction in the activity of the mitochondrial respiratory chain, and a dysregulation of the enzymes involved in the biosynthesis of coenzyme Q10 were observed in human stem-cell models. In this study, untargeted and targeted metabolome analyses were performed with MSA patient-derived GABAergic striatal medium spiny neurons focusing on the citrate cycle and mitochondrial respiratory chain. The results indicate a significant decrease in succinate and ATP as well as an imbalanced NAD⁺/NADH ratio of MSA cell lines compared to matched healthy controls, suggesting alterations in mitochondrial processes which may facilitate neurodegeneration. Full article

Depression represents a leading cause of global disability, yet its pathogenesis remains incompletely understood. This review synthesizes emerging evidence highlighting the multifaceted role of Aquaporin-4 (AQP4), the central nervous system’s predominant water channel, in the pathophysiology of depression. Preclinical studies frequently report AQP4 dysregulation in depression models, characterized by reduced perivascular expression and impaired polarization in mood-relevant brain circuits. We delineate how AQP4 impairment is implicated in depression through several interconnected mechanistic pathways: (1) exacerbating glutamate excitotoxicity by disrupting astrocytic glutamate clearance; (2) impairing monoaminergic neurotransmission and synaptic plasticity; (3) potentiating neuroinflammatory cascades; (4) inducing mitochondrial functional impairment and oxidative stress; and (5) participating in hypothalamic–pituitary–adrenal (HPA) axis dysregulation by disrupting perineuronal osmotic and ionic homeostasis in response to arginine vasopressin (AVP) signaling. Furthermore, we explore the therapeutic relevance of AQP4, noting that diverse antidepressant treatments appear to partly exert their effects by modulating AQP4 expression and function. Collectively, the evidence positions AQP4 not as a solitary causative factor, but as a critical contributing component within the broader astrocyte–neuron–immune network. We therefore propose AQP4 as a promising node for therapeutic intervention, whose modulation may help counteract core pathophysiological processes in depression, offering a potential avenue for novel treatment development. Full article

In this study, polystyrene (PS) and PS/TiO₂ nanofibers were fabricated through electrospinning and quantitatively characterized to analyze and predict fiber diameters. To advance predictive methodologies for materials design, artificial neural network (ANN) models based on multilayer perceptron (MLP) and radial basis function (RBF) architectures were developed using system- and process-level parameters as inputs and the fiber diameter as the output. Two data classes were constructed: Class 1, consisting of PS/TiO₂ nanofibers, and Class 2, containing both PS and PS/TiO₂ nanofibers. The architectural optimization of the ANN models, particularly the number of neurons in hidden layers, had a critical influence on the correlation between predicted and experimentally measured fiber diameters. The optimal MLP configuration employed 40 and 20 neurons in the hidden layers, achieving mean square errors (MSEs) of 4.03 × 10⁻³ (Class 1) and 7.01 × 10⁻³ (Class 2). The RBF model reached its highest accuracy with 30 and 250 neurons, yielding substantially lower MSE values of 1.42 × 10⁻³² and 2.75 × 10⁻³² for Class 1 and Class 2, respectively. These findings underline the importance of methodological rigor in data-driven modeling and demonstrate that carefully optimized ANN frameworks can serve as powerful tools for predicting structural features in nanostructured materials, thereby supporting rational materials design and synthesis. Full article

Insulin is an anabolic hormone involved in the regulation of several processes, such as the storage of glucose into glycogen, decrease of glucose output, stimulation of glucose transport into cells, etc. The hormone binds to its receptor, thereby activating an intracellular signaling cascade. Once activated, the insulin receptor (INSR) phosphorylates multiple intracellular substrates, which initiate the downstream signaling pathway. The nature of insulin signaling pathways may vary depending on the organ or tissue. In the central nervous system (CNS), INSRs are expressed in all cell types. This observation may suggest that insulin signaling is involved in important and diverse processes. It regulates glucose metabolism, supports cognitive functions, enhances the outgrowth of neurons, as well as plays a role in the modulation of release and uptake of catecholamine, among other roles. Importantly, insulin can freely cross the blood–brain barrier (BBB) from the circulation and is also synthesized locally within the brain. Insulin resistance (IR) impairs insulin signaling, which may accelerate brain aging, affect plasticity, and potentially contribute to neurodegeneration. Dysregulation of insulin signaling has been implicated in several diseases, including diabetes mellitus, metabolic syndrome, certain cancers, and neurodegenerative diseases, such as Alzheimer’s disease. There are two principal insulin signaling pathways: the PI3K/AKT pathway, primarily associated with metabolic effects, and the MAPK pathway, which is involved in cell growth, survival, and gene expression. Our review describes the role of insulin in the human brain, as well as the disturbances in insulin signaling resulting from brain insulin resistance, with a particular focus on its association with Alzheimer’s disease. Full article

The blood–brain barrier and blood–spinal cord barrier (BBB/BSCB) are essential protective components for the healthy functioning of the central nervous system (CNS). While these barriers protect the CNS from peripheral factors, such as immune cells and blood products, they can become disrupted in pathological conditions and injury. The neurovascular unit (NVU) is composed of endothelial cells (ECs), pericytes, astrocytes, microglia, and neurons, all of which contribute to proper function and the maintenance of the BBB/BSCB. Tight junctions (TJs) unite cellular components and are modulated by both intrinsic and extrinsic factors. Systemic processes, such as pain (nociceptive activity), inflammation, and blood hemostasis, can impact BBB/BSCB function, often leading to a disrupted barrier and increased peripheral infiltration. This, in turn, can increase neuroinflammation and drive microglia activation, progressive hemorrhagic necrosis (PHN), and matrix metalloproteinase (MMP) activity. Targeting these processes and mitigating the deleterious effects of BBB/BSCB breakdown represents a key therapeutic target after neural injury and other pathological conditions. Full article

This paper addresses a central conceptual challenge in Quantum-like Cognition and Decision-Making (QCDM) and the broader research program of Quantum-like Modeling (QLM): the interpretation of phases in quantum-like state superpositions. In QLM, system states are represented by normalized vectors in a complex Hilbert space, $|\psi ⟩={\sum }_k{X}_k|k⟩$, where the squared amplitudes $P_k={\left|X_k\right|}^2$ are outcome probabilities. However, the meaning of the phase factors $e^{i{\varphi }_k}$ in the coefficients $X_k=P_k{e}^{i{\varphi }_k}$ has remained elusive, often treating them as purely phenomenological parameters. This practice, while successful in describing cognitive interference effects (the "interference of the mind”), has drawn criticism for expanding the model’s parameter space without a clear physical or cognitive underpinning. Building on a recent framework that connects QCDM to neuronal network activity, we propose a concrete interpretation. We argue that the phases in quantum-like superpositions correspond directly to the phases of random oscillations generated by neuronal circuits in the brain. This interpretation not only provides a natural, non-phenomenological basis for phase parameters within QCDM but also helps to bridge the gap between quantum-like models and classical neurocognitive frameworks, offering a consistent physical analogy for the descriptive power of QLM. Full article

Serotonin (5-HT) performs a wide range of neuromodulatory actions in the nervous system, including the regulation of the neurons that release it, by activation of several types of autoreceptors that modulate their electrical activity, as well as its own release. 5-HT neurons release serotonin in different manners from different subcellular structures, including the presynaptic terminals, the somatodendritic region and the axons. The different releasing structures of the same neurons have different types of autoreceptors, which exert differential auto-regulatory effects. Here we critically review the evidence of serotonergic autoregulation, both in mammals and in invertebrates, with particular emphasis on studies of serotonergic Retzius neurons of the leech, which have been a model for detailed studies of serotonin secretion from different neuronal structures. In these neurons serotonin produces different and even opposite effects on different releasing structures, such as the presynaptic terminals and the soma, through activation of different types of autoreceptors, thus increasing the specialization of the mechanisms that regulate exocytosis from each site. The differential autoregulation of serotonin release from different structures enables a single neuron to exert a variety of different functions in the nervous system. Full article

The red imported fire ant, Solenopsis invicta Buren, is a eusocial insect that relies on a sophisticated chemical communication system for colony organization and function. Its olfactory system is vital for detecting semiochemicals in the environment. This study utilized single sensillum recording (SSR) to assess the olfactory neuronal responses of female alates and workers from basiconica sensilla exposed to a panel of 62 individual pheromones and general odorants, including terpenes, terpenoids, pyrazines, pyridines, ketones, aldehydes, alcohols, acids, aliphatic and aromatic acetates, benzoates, benzyl esters, and three essential oils. Basiconica sensilla, which contain multiple olfactory receptor neurons (ORNs), exhibited moderate to strong responses to most of the tested compounds, demonstrating a broad sensitivity to all odorants elevated. Comparative analysis of the two castes revealed that ORNs had similar responses to 47 odorants; however, workers showed stronger responses to nine specific compounds, while female alates responded more strongly to six others. These differences underscore the caste-specific olfactory tuning, likely reflecting their distinct roles within the colony. This study presents the first comprehensive mapping of basiconica sensilla responses to general odorants in S. invicta female alates and workers, enhancing our understanding of the S. invicta chemical ecology and potentially contribute to more effective fire ant management strategies. Full article

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases that, despite the availability of symptomatic and modestly beneficial treatments, still lack therapies capable of halting disease progression. A histopathological hallmark of both diseases is the cytoplasmic deposition of TDP-43 in neurons, which is attributed to both intrinsic (e.g., mutations, aberrant cleavage) and extrinsic factors (e.g., prolonged oxidative stress, impaired clearance pathways). Mutations and certain PTMs (e.g., cysteine oxidation) destabilize RNA binding, promoting monomer misfolding and increasing its half-life. Disruptions to core ubiquitin-proteasome system (UPS) subunits impede efficient processing, contributing to the clearance failure of misfolded TDP-43 monomers. The accumulation of monomers drives phase separation within stress granules, creating nucleation hotspots that eventually bypass the thermodynamic barrier, resulting in exponential growth. This rapid growth then culminates in the failure of the autophagy-lysosome pathway (ALP) to contain the aggregation, resulting in a self-sustaining feed-forward loop. Here, we organize these factors into a conceptual kinetic cascade that links TDP-43 misfolding, phase separation, and clearance failure. Therapeutic strategies must therefore move beyond simple clearance and focus on targeting these kinetic inflection points (e.g., oligomer seeding, PTM modulation). Full article

Neurodegeneration is closely linked to neuroinflammation and is frequently accompanied by comorbidities with inflammatory features. Tripartite motif (TRIM) proteins are known to play an important role in innate immunity and inflammatory signaling in various tissues and organs of the body, including the central nervous system. Among the main cell types of the brain, TRIMs’ functions in microglia are largely associated with the regulation of intracellular inflammatory signaling, while in neurons they mainly relate to cell survival and oxidative stress. Data concerning TRIMs’ activity in astrocytes remain limited. Many TRIM proteins exert similar pro- or anti-inflammatory effects in neuroinflammation and in other inflammatory disorders in the body, although for some members their roles are reported to be opposite, contradictory, or insufficiently characterized, highlighting the need for further research. The aim of this review was to summarize published data on the common mechanisms of TRIMs’ actions as modulators of inflammation, and compare available reports in the context of neuroinflammation and peripheral inflammatory pathologies. We suggested that such an analysis may be valuable for guiding future research—both by identifying existing gaps in knowledge and by supporting the rational selection of specific TRIM proteins for investigation as therapeutic targets, with careful consideration of their systemic effects. Full article

Neuromorphic computing, an interdisciplinary field combining neuroscience and computer science, aims to create efficient, bio-inspired systems. Different from von Neumann architectures, neuromorphic systems integrate memory and processing units to enable parallel, event-driven computation. By simulating the behavior of biological neurons and networks, these systems excel in tasks like pattern recognition, perception, and decision-making. Neuromorphic computing chips, which operate similarly to the human brain, offer significant potential for enhancing the performance and energy efficiency of bio-inspired algorithms. This review introduces a novel five-dimensional comparative framework—process technology, scale, power consumption, neuronal models, and architectural features—that systematically categorizes and contrasts neuromorphic implementations beyond existing surveys. We analyze notable neuromorphic chips, such as BrainScaleS, SpiNNaker, TrueNorth, and Loihi, comparing their scale, power consumption, and computational models. The paper also explores the applications of neuromorphic computing chips in artificial intelligence (AI), robotics, neuroscience, and adaptive control systems, while facing challenges related to hardware limitations, algorithms, and system scalability and integration. Full article

Background: The mirror neuron system (MNS) has been proposed as a key neural mechanism linking action perception, motor representation, and social cognition. This framework has increasingly been applied to pain research, encompassing pain empathy, observational learning of pain, and rehabilitative interventions such as mirror therapy. However, the literature is conceptually heterogeneous, methodologically diverse, and spans experimental, social, and clinical domains. Objective: This scoping review aims to map the extent, nature, and characteristics of the available evidence on the relationship between the MNS and pain, clarifying how MNS-related mechanisms are defined, investigated, and applied across different contexts. Methods: A scoping review was conducted using the methodological framework proposed by the Joanna Briggs Institute and reported in accordance with PRISMA-ScR guidelines. We searched PubMed/MEDLINE, Scopus, Web of Science, and PsycINFO. Studies were included if they addressed MNS-related mechanisms in pain processing, pain empathy, pain modulation, or pain rehabilitation. Eligible studies were charted and synthesized descriptively and thematically. Results: Twenty-one studies met the inclusion criteria. The evidence was predominantly derived from clinical and rehabilitative settings, with most studies focusing on mirror therapy or mirror visual feedback interventions. The majority of included populations consisting of adults with chronic pain conditions, particularly phantom limb pain and complex regional pain syndrome. Pain intensity, assessed mainly through self-reported clinical scales, was the most frequently reported outcome. A smaller number of studies investigated action observation or motor imagery paradigms, primarily in chronic musculoskeletal pain, showing short-term hypoalgesic effects. Across studies, substantial heterogeneity was observed in the conceptualization of MNS-related constructs, intervention protocols, outcome measures, and follow-up duration. Conclusions: Despite extensive theoretical discussion of the MNS, empirical applications are largely confined to clinical mirror-based interventions, with limited use of direct neurophysiological or neuroimaging markers. Since crucial conceptual and methodological gaps constrain comparability and translation into clinical practice, there is a need for clearer operational definitions and more integrated experimental and clinical research approaches. Full article

Spinal cord injury (SCI) remains a major clinical challenge due to the limited regenerative capacity of the central nervous system (CNS). Effective scaffolds for repair must combine mechanical compatibility with host tissue, controlled degradation matching the time course of regeneration, and microarchitectural features that promote neuronal survival. Electrospun nanofibrous scaffolds mimic the structural and mechanical features of the extracellular matrix, providing critical cues for neuronal adhesion and glial modulation in neural regeneration. Here, we fabricated biodegradable poly(lactic acid)/poly(ε-caprolactone) (PLA/PCL) scaffolds using a dichloromethane/tetrahydrofuran (DCM/THF) solvent system to induce surface porosity via solvent-driven phase separation. The DCM/THF solvent system formulation produced nanofibers with porous surfaces and increased area for cell interaction. PLA/PCL scaffolds showed a Young’s modulus of ~26 MPa and sustained degradation, particularly under oxidative conditions simulating the post-injury microenvironment. In vitro, these scaffolds enhanced neuronal density up to fivefold and maintained ~80% viability over 10 days in primary neuron–glia cultures. Morphometric analysis revealed that DCM/THF-based scaffolds supported astrocytes with preserved process complexity and reduced circularity, indicative of a less reactive morphology. In contrast, scaffolds fabricated with 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) displayed reduced bioactivity and promoted morphological features associated with astrocyte reactivity, including cell rounding and process retraction. These findings demonstrate that solvent-driven control of scaffold microarchitecture is a powerful strategy to enhance neuronal integration and modulate glial morphology, positioning DCM/THF-processed PLA/PCL scaffolds as a promising platform for CNS tissue engineering. Full article

Background/Objectives: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders. Despite its multifactorial etiology, PD pathophysiology shared specific features such as cytoplasmic α-synuclein inclusions, oxidative stress, mitochondrial dysfunction, and impaired autophagy. Bromodomain and Extra-Terminal domain (BET) proteins, functioning as epigenetic readers, have recently emerged as promising therapeutic targets due to their regulatory role in redox homeostasis, neuroinflammation, and autophagy. However, their potential involvement in PD pathophysiology remains largely unexplored. Therefore, we aimed at evaluating whether BET modulation could ameliorate the parkinsonian phenotype in two cellular models. Methods: Differentiated SH-SY5Y and N1E-115 neuronal cells were exposed to rotenone toxin to mimic PD phenotype and co-treated with the small BET inhibitor JQ1. Results: BET inhibition significantly counteracted rotenone-induced cell death, neuromorphological alterations, and α-synuclein accumulation. These protective effects were accompanied by restoration of redox balance, as indicated by enhanced activation of the antioxidant system and suppression of the pro-oxidant NADPH oxidase complex. Moreover, JQ1 treatment alleviated mitochondrial dysfunction and corrected autophagy impairments triggered by rotenone. Conclusions: These data highlight a novel role for BET proteins in neurodegeneration, suggesting that their modulation may represent a promising approach to counteract PD neuropathology. Full article

Bidirectional communication between the central nervous system and the immune system is crucial for brain function, particularly in regulating neuroplasticity: on the one hand, glial cells modulate neuronal function, brain circuitry, axon myelination, dendritic spine architecture, and information processing, while on the other hand, neuronal activity can alter the immune response. Neuroinflammation and dysregulation of astroglia and microglia can be detrimental to brain development and function. In particular, maladaptive responses and chronic glial activation have been correlated to synaptic dysfunction in diverse brain conditions. In the present review, we will provide a general introduction to the main players of the neuroimmune response and their ability to modulate neuroplasticity, followed by a comprehensive overview of experimental evidence linking the dysregulation of immune mediators to the disruption of synaptic plasticity in neurodegenerative and neurodevelopmental disorders, with a specific focus on Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder. Full article