Search Results (1,219)

The adult lumbar spinal cord plays a critical role in locomotor control and somatosensory integration, whose transcriptional architecture under physiological conditions has been characterized in various studies with restricted numbers of individuals (up to four). Here, we present an integrative single-nucleus RNA sequencing (snRNA-seq) atlas of the healthy adult mouse lumbar spinal cord, assembled from over 86,000 nuclei from 16 samples across five public datasets. Using a harmonized computational pipeline, we identify all major spinal cell lineages and resolve 17 transcriptionally distinct neuronal subtypes. A central novelty of our approach is the systematic inclusion of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and pseudogenes. By comparing transcriptomic analyses based on coding-only, non-coding-only, and combined gene sets, we show that ncRNAs, despite accounting to a 10% of the recorded information of each cell, contribute to cell type-specific signatures. This resource offers a high-resolution, ncRNA-inclusive reference for the adult spinal cord and provides a foundation for future studies on spinal plasticity, injury, and regeneration. Full article

Accurate and feasible target assignment in an urban environment without road networks remains challenging. Existing methods exhibit critical limitations: computational inefficiency preventing real-time decision-making requirements and poor cross-scenario generalization, yielding task-specific policies that lack adaptability. To achieve efficient target assignment in urban adversarial scenarios, we propose an efficient traversable path generation method requiring only binarized images, along with four key constraint models serving as optimization objectives. Moreover, we model this optimization problem as a Markov decision process (MDP) and introduce the generalization sequential proximal policy optimization (GSPPO) algorithm within the reinforcement learning (RL) framework. Specifically, GSPPO integrates an exploration history representation module (EHR) and a neuron-specific plasticity enhancement module (NPE). EHR incorporates exploration history into the policy learning loop, which significantly improves learning efficiency. To mitigate the plasticity loss in neural networks, we propose an NPE module, which boosts the model’s representational capability and generalization across diverse tasks. Experiments demonstrate that our approach reduces planning time by four orders of magnitude compared to the online planning method. Against the benchmark algorithm, it achieves 94.16% higher convergence performance, 33.54% shorter assignment path length, 51.96% lower threat value, and 40.71% faster total time. Our approach supports real-time military reconnaissance and will also facilitate rescue operations in complex cities. Full article

Short-term synaptic plasticity (STSP) and short-term neuronal dynamics (STND) are fundamental properties of neural circuits, essential for information processing and brain function. Emerging evidence suggests that biological sex may influence these properties, yet sex-related differences in STSP and STND remain underexplored. This study investigates sex-specific differences in short-term synaptic plasticity (STSP) and neuronal dynamics (STND) along the dorsoventral axis of the rat hippocampus. Our findings reveal that both STSP and STND exhibit significant variation between female and male subjects. These differences are particularly pronounced in the ventral hippocampus, a region associated with affective and motivational processes. Given the role of short-term activity-dependent neuronal phenomena in modulating information processing and network function, these findings suggest potential functional implications for sex-specific cognitive and emotional regulation. The results highlight the importance of incorporating sex as a biological variable in studies of hippocampal physiology and its relation to behavior. Full article

Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in neural progenitor cells, mature neurons, and glial populations. In neural stem and progenitor cells, HDACs modulate neurogenesis, fate specification, and lineage commitment. In differentiated neurons, HDACs govern synaptic plasticity, memory formation, and survival. In glial cells, including astrocytes and microglia, HDACs orchestrate inflammatory responses, redox balance, and metabolic adaptations. We further examine the dysregulation of HDAC expression and activity in major neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Evidence from human post-mortem brain studies reveals region- and isoform-specific alterations in HDAC expression, which are closely associated with cognitive decline, mitochondrial dysfunction, and neuroinflammation. Preclinical studies support the use of HDAC inhibitors (HDACi) as neuroprotective agents, capable of restoring acetylation homeostasis, reducing neuroinflammation, and improving neuronal function. Given the relevance of HDACi, we summarize current clinical studies assessing the safety of these compounds in the context of tumor biology, as well as their potential future applications in neurodegenerative diseases. Together, this review underscores the dual significance of HDACs as biomarkers and therapeutic targets in the context of CNS disorders. Full article

Neurodevelopmental disorders (NDDs), including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID), and tic disorders, comprise a range of conditions that originate in early childhood and impact cognitive, behavioral, and social functioning. Despite their clinical heterogeneity, they often share common molecular and neurobiological framework. This narrative review aims to examine the role of neurotrophins—particularly the brain-derived neurotrophic factor, nerve growth factor, and related molecules—in the pathophysiology of NDDs, and to explore their potential as biomarkers and therapeutic targets. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, including both clinical and preclinical studies. Neurotrophins are critically involved in brain development, influencing neurogenesis, synaptic plasticity, and neuronal survival. Dysregulation in their signaling pathways has been associated with core features of ASD and ADHD and may modulate cognitive outcomes in ID. Emerging evidence also supports a role for neuroimmune interactions and neurotrophic dysfunction in tic disorders. However, findings across studies remain inconsistent due to methodological variability and limited longitudinal data. Future research should aim for standardized methodologies and stratified, longitudinal designs to clarify their role across developmental stages and clinical phenotypes. Full article

Insulin-like growth factor I (IGF-I) is a neurotrophic factor that regulates neurogenesis, synaptogenesis, and neuronal survival. It also enhances neuronal activity and facilitates synaptic plasticity. Additionally, IGF-I plays a critical role in the regulation of metabolism in mammals. Emerging evidence indicates that IGF-I modulates sleep architecture. The circadian integration of metabolic and neuronal systems serves to optimize energy utilization across the light/dark cycle. Current data suggest that IGF-I may be a key mediator of this integration, promoting brain activity during wakefulness, a state that coincides with increased metabolic demand. In this review, we summarize recent findings on the interplay between metabolism, IGF-I, and brain activity. Full article

Chronic pain is a complex and persistent condition involving sustained nociceptive input, maladaptive neuroplastic changes, and neuroimmune interactions. Central to its pathophysiology is the dysregulation of neuromodulatory signaling pathways, including neurotransmitters (e.g., dopamine, serotonin, norepinephrine), neuropeptides (e.g., substance P, CGRP), and neurotrophic factors (e.g., BDNF), which modulate both central and peripheral sensitization mechanisms. In disorders such as fibromyalgia, altered monoaminergic transmission has been implicated in the attenuation of descending inhibitory control, thereby enhancing pain perception and reducing responsiveness to conventional therapies. Concurrently, neuroinflammation, driven by glial cell activation and cytokine release, further exacerbates neuronal excitability and reinforces maladaptive signaling loops. Recent technological advances, including transcriptomic profiling, functional neuroimaging, and single-cell RNA sequencing, have provided new insights into patient-specific patterns of neuromodulatory dysfunction, highlighting potential biomarkers for disease stratification and therapeutic targeting. These developments support the hypothesis that dysregulated neuromodulatory circuits not only underlie diverse chronic pain phenotypes but may also serve as intervention points for precision medicine. This narrative review synthesizes current evidence on the roles of neuromodulatory systems in chronic pain, focusing on synaptic plasticity, nociceptor sensitization, and neuroimmune crosstalk. By integrating preclinical findings with clinical observations, we propose a mechanistic framework for understanding pain chronification and guiding future therapeutic strategies. Harnessing neuromodulatory targets, whether pharmacologically or via neuromodulation technologies, could offer more personalized and effective approaches to chronic pain management. Full article

Cardiotonic steroids (CTS), including the endogenous compound ouabain, modulate neuronal Na/K-ATPase (NKA) activity in a concentration-dependent manner, affecting neuronal survival and function. While high concentrations of ouabain are neurotoxic, endogenous levels of 0.1–1 nM exert neuroprotective effects and influence intracellular signaling. However, the effects of physiologically relevant ouabain concentrations on excitatory synaptic transmission remain unclear. In this study, we examined how 1 nM ouabain affects synaptic responses in rat hippocampal CA1 neurons. Using whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSCs) and extracellular recordings of field excitatory postsynaptic potentials (fEPSPs), we found that ouabain enhances excitatory synaptic transmission, increasing EPSC amplitude and fEPSP slope by 35–50%. This effect was independent of NMDA receptor (NMDAR) activity. Ouabain reduced the magnitude of NMDAR-dependent long-term potentiation (LTP), but still augmented fEPSPs when applied after LTP induction. This implies separate additive mechanisms. These observations exhibit that ouabain, at concentrations corresponding to endogenous levels, facilitates basal excitatory synaptic transmission while partially suppressing LTP. We propose that ouabain exerts dual modulatory effects in hippocampal networks via distinct synaptic mechanisms. Full article

The neuropeptide oxytocin (OXT) is involved in social bonding, reproduction, and childbirth. Its activity is mediated by the oxytocin receptor (OXTR), also expressed in the skin. OXT alleviates dermal fibroblast senescence, and OXT levels correlate with visible skin aging. OXT inhibits nociceptive signaling and promotes neuronal plasticity. Here, we demonstrate OXT-like benefits of OXTR activation for skin touch sensoriality and nociception, as well as visible skin health and beauty indicators, using an aqueous extract of Hyacinthus orientalis bulbs. OXTR activation was evaluated in a Chinese hamster ovary (CHO) cell model. Nociception and innervation benefits were investigated in keratinocyte/sensory neuron coculture models. A placebo-controlled clinical study evaluated gentle touch receptivity, nociception, skin tone, elasticity, and wrinkling. The extract activated OXTR and enhanced dermal fibroblast proliferation in vitro. In the keratinocyte-neuron coculture, the HO extract lowered nociceptive CGRP release below that of the unstimulated and OXT controls and promoted neuronal survival and dendricity. An organ-on-a-chip coculture showed decreased electrical activity and increased neuronal peripherin. Clinically, we observed selective left-side frontal alpha-wave activation, indicating pleasant sensation, reduced nociception, enhanced skin glow, improved elasticity, and reduced wrinkling. This extract thus shows high value for holistic wellbeing solutions, enhancing the skin’s receptivity to pleasant sensations and promoting well-aging. Full article

Ducks exhibit substantial ecological and dietary diversity, which drives morphological and functional adaptations in their digestive systems. This study analyzed the small intestine and cecum of three wild duck species: Mallard (Anas platyrhynchos), Tufted Duck (Aythya fuligula), and Green-Winged Teal (Anas crecca) collected post-mortem. Histomorphometric analysis and immunohistochemistry (IHC) with the pan-neuronal marker HuC/D were performed. The Tufted Duck showed the thickest intestinal muscle layers, particularly in the duodenum and ileum, and the largest enteric ganglia, indicating adaptation to a fibrous and protein-rich diet. The Mallard displayed the longest villi and deepest crypts, consistent with its omnivorous diet rich in plant material. The Green-Winged Teal, which consumes highly digestible insect-rich food, had the shortest villi and thinnest muscle layers. Differences in enteric ganglion size and organization among species suggest varying neuroregulatory demands in different gut segments. These findings confirm that intestinal morphology and enteric nervous system (ENS) structure are tightly linked to dietary specialization and ecological strategies. The results highlight the high adaptive plasticity of the avian digestive system in response to feeding behavior. Full article

Bisphenol A (BPA) and bisphenol S (BPS) are frequently used in the plastic industry. Despite significant alimentary exposure, their effects on the gastrointestinal (GI) tract remain largely unknown. Cholinergic and/or purinergic neurotransmission facilitates GI tract motility and secretion, indirectly controlling the absorption and toxicity of xenobiotics. Hence, this study examined the neurochemical effects of BPA and BPS in the tripartite cholinergic myenteric synapse of CD1 mice colon. Short time exposure to both bisphenols showed a partial loss of VAChT-positive neurons and Ano-1-positive interstitial cells of Cajal (ICCs), without affecting the amount of glial cells labelled with S100β. Both bisphenols reduced the spontaneous myographic activity and the release of [³H]acetylcholine ([³H]ACh) and adenosine from stimulated myenteric neurons and pacemaker ICCs, respectively, without affecting the outflow of ATP. Overall data suggest that both bisphenols inhibit the cholinergic neurotransmission of CD1 mice colon by affecting the amount and/or function of ICCs at the tripartite myenteric synapse. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN), leading to motor impairments and numerous non-motor manifestations, including anxiety. Notably, anxiety has been shown to exacerbate disease progression and hinder treatment outcomes in PD. Botulinum neurotoxin (BoNT), recognized for its ability to block excessive release of acetylcholine (ACh), has been shown to provide clinical effectiveness in managing motor symptoms. BoNT appears to enhance neuroregenerative plasticity and mitigate neuroinflammation through mechanisms speculated to extend beyond its classical mode of action. Nevertheless, reports on its potential anxiolytic and neuroprotective effects in PD remain limited. Aim: This study investigated the effect of BoNT on motor and anxiety-like behaviors in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Methods: The experimental animals were assessed for behavioral changes using the open field test (OFT), rotarod, pole test, light-dark box test (LDBT), and elevated plus maze (EPM). Immunohistochemistry was employed to enumerate tyrosine hydroxylase (TH)-positive dopaminergic neurons and ionized calcium-binding adapter molecule (Iba)-1 expressing microglia in SN. Results: BoNT treatment markedly alleviated motor deficits and anxiety. Quantification of TH- and Iba-1-positive cells revealed that BoNT promotes neuroprotection and minimizes microglial burden in the SN of the PD model. Conclusions: The outcome of the study represents the anxiolytic, neuroprotective, and microglial modulatory potentials of BoNT in PD, supporting its therapeutic promise beyond the management of motor symptoms. Given its multifaceted properties, BoNT can be considered a potential therapeutic candidate for PD and other neurological disorders. Full article

CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell–extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflammation, and synaptic plasticity. In microglia and macrophages, CD44 mediates immune signaling and phagocytic activity, and it is dynamically upregulated in neuroinflammatory diseases, particularly through pathways involving Toll-like receptor 4. CD44 expression in astrocytes is abundant during central nervous system development and in diseases, contributing to glial differentiation, reactive astrogliosis, and scar formation. Though its expression is less prominent in mature neurons, CD44 supports neural plasticity, circuit organization, and injury-induced repair mechanisms. Additionally, its expression at nervous system barriers, such as the blood–brain barrier, underscores its role in regulating vascular permeability during inflammation and ischemia. Collectively, CD44 emerges as a critical integrator of neural cell function and intercellular communication. Although the roles of CD44 in glial cells appear to be similar to those explored in other tissues, the expression of this molecule and its variants on neurons reveals peculiar functions. Elucidating the cell-type-specific roles and regulation of CD44 variants may offer novel therapeutic strategies for diverse neurological disorders. Full article

α-Cyclodextrin/Moringin (α-CD/MOR) is an isothiocyanate showing neuroprotective and antioxidant properties. In this work, we studied in differentiated NSC-34 motor neurons cell line the molecular pathways activated following a treatment of 96 h with α-CD/MOR at different doses, namely 0.5, 5 and 10 μM. Taking advantage of comparative transcriptomic analysis, we retrieved the differentially expressed genes (DEGs) and we mapped DEGs to synaptic genes using the SynGO database. Then, we focused on the biological pathways in which they are involved. We observed that the prolonged treatment with α-CD/MOR significantly modulated biological processes and cellular components associated with synaptic organization. Interestingly, the KEGG pathway “Regulation of actin cytoskeleton” was overrepresented, alongside pathways related to synapses and axon guidance. Specifically, SPIA analysis indicated that the “Regulation of actin cytoskeleton” pathway was found to be activated with the highest dose of α-CD/MOR. Moreover, α-CD/MOR also modulated transcription factors involved in synaptic plasticity, such as Creb1. These results could indicate that α-CD/MOR can influence synaptic functions and organization, being involved in synaptic plasticity through the modulation of actin dynamics. Full article

Alzheimer’s disease (AD) and major depressive disorder (MDD) are prevalent central nervous system (CNS) disorders that share overlapping symptoms but differ in underlying molecular mechanisms. Distinguishing these mechanisms is essential for developing targeted diagnostic and therapeutic strategies. In this study, we integrated multi-tissue transcriptomic datasets from brain and peripheral samples to identify differentially expressed microRNAs (miRNAs) in AD and MDD. Functional enrichment analyses (KEGG, GO) revealed that dysregulated miRNAs in AD were associated with MAPK, PI3K–Akt, Ras, and PD-1/PD-L1 signaling, pathways linked to synaptic plasticity, neuroinflammation, and immune regulation. In contrast, MDD-associated miRNAs showed enrichment in Hippo signaling and ubiquitin-mediated proteolysis, implicating altered neurogenesis and protein homeostasis. Network analysis highlighted key disease- and tissue-specific miRNAs, notably hsa-miR-1202 and hsa-miR-24-3p, with potential roles in neuronal survival and molecular network regulation. These findings suggest that miRNAs may serve as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring in both disorders. While therapeutic targeting of miRNAs offers promise, challenges such as blood–brain barrier penetration and tissue-specific delivery remain. This integrative approach provides a translational framework for advancing miRNA-based strategies in CNS disease research. Full article