Frontiers In Cellular Neuroscience[JOURNAL]
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200 papers
Correction: Acetylcholine receptor stimulation activates protein kinase C mediated internalization of the dopamine transporter.
Underhill SM, Amara SG
Front Cell Neurosci · 2026 · PMID 42396565 · Full text
[This corrects the article DOI: 10.3389/fncel.2021.662216.].
[This corrects the article DOI: 10.3389/fncel.2021.662216.].
Defining spinal motor neuron subtypes across development: from embryonic specification to postnatal maturation.
Blauth O, Sławińska U, Zawadzka M
Front Cell Neurosci · 2026 · PMID 42396564 · Full text
Spinal motor neurons are essential for translating neural activity into coordinated muscle contraction, yet defining their functional subtypes across development remains a persistent challenge. While embryonic patterning...
Spinal motor neurons are essential for translating neural activity into coordinated muscle contraction, yet defining their functional subtypes across development remains a persistent challenge. While embryonic patterning establishes the initial positional and molecular framework of motor neuron identity, substantial refinement continues during early postnatal life as intrinsic electrophysiological properties, synaptic connectivity, and neuromuscular interactions mature. A major limitation in the field is the lack of temporally stable and functionally validated molecular markers that can reliably distinguish motor neuron subtypes across developmental stages, particularly during neonatal maturation when subtype-specific physiological features are emerging. In this review, we synthesize classical developmental studies with recent advances in single-cell transcriptomics, chromatin accessibility profiling, and multimodal approaches linking gene expression with electrophysiological and anatomical features. Focusing on lumbar spinal motor neurons that underlie locomotor behavior, we discuss how transcriptional programs, activity-dependent mechanisms, and non-cell-autonomous signals converge to shape subtype-specific maturation trajectories. We propose that motor neuron subtype identity is best understood as a dynamic molecular and physiological state shaped by developmental timing, circuit context, and activity-dependent mechanisms, rather than as a fixed category defined by a single marker. From this perspective, early postnatal life represents a sensitive window of identity consolidation during which molecular programs and functional properties become aligned. Establishing temporally robust subtype markers and integrating molecular and physiological datasets will be essential for resolving motor neuron diversity and for improving our understanding of subtype-selective vulnerability in neuromuscular diseases. While this review emphasizes embryonic and early postnatal development, understanding how molecular subtypes stabilize in the adult spinal cord, despite ongoing activity-dependent physiological plasticity, remains an essential reference point for defining temporally robust motor neuron identities.
Brief mechanical pulses induce sustained intracellular L-lactate production in astrocytes.
Belko Parkel K, Kuhanec D, Gržina ŽT … +3 more , Haque Chowdhury H, Zorec R, Kreft M
Front Cell Neurosci · 2026 · PMID 42389485 · Full text
Intracranial-pressure transients impose mechanical strain on perivascular astrocytes, but it is unclear whether brief mechanical events elicit metabolic responses. Here, we applied 1.5-s pressure-driven mechanical stimul...
Intracranial-pressure transients impose mechanical strain on perivascular astrocytes, but it is unclear whether brief mechanical events elicit metabolic responses. Here, we applied 1.5-s pressure-driven mechanical stimuli (5-1,000 hPa) to cultured primary rat cortical astrocytes using a patch-micropipette microinjector and monitored cytosolic lactate ([lactate]) with a Förster resonance energy transfer Laconic nanosensor. Single pressure pulses (5-1,000 hPa) evoked a pressure-dependent increase in [lactate] that persisted for minutes after stimulation, reaching a steady-state increase of 0.3-4.1% relative to baseline over 200-300 s. Sequential pulses delivered to the same cell produced transient spikes followed by stepwise increases in the post-stimulus plateau, yielding an estimated activation threshold of ~4-5 hPa. Transient receptor-potential vanilloid-4 (TRPV4) immunoreactivity was detected in cultured astrocytes, and pharmacologic inhibition of TRPV4 with HC-067047 attenuated mechanically evoked lactate accumulation during mechanical stimulation by solution bolus addition. These findings demonstrate that astrocytes convert brief mechanical stimuli into prolonged cytosolic lactate increases, supporting a contribution of TRPV4-associated mechanosensitive signaling to astrocytic mechano-metabolic integration.
Effects of ethanol leaf extract of on scopolamine-induced hippocampal neurodegeneration in adult male Wistar rats: evidence from behavioral, biochemical, histological, and immunohistochemical analyses.
Ale TM, Arayombo BE, Sloh AW
Front Cell Neurosci · 2026 · PMID 42382986 · Full text
Previous studies have demonstrated that phytochemicals present in leaves possess neuro-regenerative and neuroprotective potentials. This study therefore evaluated the effects of ethanol leaf extract of (ELESM) on the h...
Previous studies have demonstrated that phytochemicals present in leaves possess neuro-regenerative and neuroprotective potentials. This study therefore evaluated the effects of ethanol leaf extract of (ELESM) on the hippocampus of adult male Wistar rats with scopolamine-induced neurodegeneration using biochemical, behavioral, histological, and immunohistochemical assessments. This study was conducted for a period of 71 days. Forty-two adults male Wistar rats (200 ± 20 g) were randomly assigned into six groups ( = 7). Group I received normal saline (1 mL/kg) orally for 10 weeks. Neurodegeneration was induced in Groups II-VI by intraperitoneal administration of scopolamine (1 mg/kg) for two weeks. Twenty-four hours after induction, Group II received normal saline (1 mL/kg) orally, Group III received donepezil (5 mg/kg) orally, while Groups IV-VI received ELESM (200, 400, and 600 mg/kg) respectively for eight weeks. Result showed that scopolamine administration significantly increased acetylcholinesterase activity, reduced antioxidant status, and promoted inflammation. Behavioral assessments showed reduced locomotor activity, anxiety-like behavior accompanied with impaired working memory. Histological findings demonstrated features of neurodegeneration, including reduced neuronal density in the dentate gyrus and a decreased proportion of healthy neurons in the cornu ammonis subfields. White matter integrity in the alveus was compromised, appearing distorted and de-compacted. Immunohistochemical analysis further revealed astrocytic reactivity in response to oxidative stress. These findings indicate that scopolamine triggered molecular and structural alterations that persisted beyond the induction period. However, treatment with Donepezil and ELESM 200 mg/kg, 400 mg/kg and 600 mg/kg produced significant anticholinesterase, antioxidant, and anti-inflammatory effects, restoring these protein levels to near normal. Donepezil and ELESM improved cognitive and memory functions and attenuated anxiety-like behavior. Histological integrities of the hippocampus subfields were preserved, while immunohistochemistry showed modulation of astrocytic glial fibrillary acidic protein expression. Chronic scopolamine administration caused long term impairments, but ELESM demonstrated neuroprotective effects against scopolamine-induced neurodegeneration, likely mediated through its anticholinesterase, antioxidant, and anti-inflammatory properties in adult male Wistar rats.
Ferroptosis in intracerebral hemorrhage: a bibliometric overview of mechanisms and future directions.
Yang H, Cui X, Liu Y … +7 more , Guo Z, Yang S, Wang J, Zhu P, Wang X, Wang X, Wang X
Front Cell Neurosci · 2026 · PMID 42382985 · Full text
INTRODUCTION: Research on ferroptosis in intracerebral hemorrhage (ICH) has expanded rapidly in recent years, but the overall knowledge structure and research trends of this field remain unclear. METHODS: A total of 254...
INTRODUCTION: Research on ferroptosis in intracerebral hemorrhage (ICH) has expanded rapidly in recent years, but the overall knowledge structure and research trends of this field remain unclear. METHODS: A total of 254 publications related to ferroptosis in ICH from the Web of Science Core Collection and Scopus databases (2014-2025) were analyzed using Bibliometrix, VOSviewer, and CiteSpace. Bibliometric analyses were performed to evaluate publication trends, research hotspots, collaboration networks, and emerging themes. RESULTS: Publication output increased markedly after 2020, reflecting growing attention to ferroptosis-related brain injury after ICH. China contributed nearly 80% of the publications, although international collaboration remained relatively limited. Keyword evolution and co-citation analyses showed that the research focus gradually shifted from general cell death pathways toward more specific mechanisms involving iron metabolism, lipid peroxidation, GPX4-mediated antioxidant regulation, and neuroinflammation. Several highly cited studies published after 2017 played important roles in shaping the development of this field. Recent studies have increasingly focused on downstream pathological processes and potential therapeutic strategies. DISCUSSION: This study summarizes the major research themes and evolving directions of ferroptosis research in ICH and provides a useful reference for future mechanistic and translational studies.
, encoding Na 1.2 channel, contributes to tonotopic maturation of spike kinetics in developing mouse MNTB.
Contreras J, Bae HG, Kim JH
Front Cell Neurosci · 2026 · PMID 42382984 · Full text
INTRODUCTION: , encoding the voltage-gated sodium channel Na 1.2, is a high-risk gene associated with autism spectrum disorder (ASD) and has been linked to sensory hypersensitivity. Recent work indicates that Na 1.2 lo...
INTRODUCTION: , encoding the voltage-gated sodium channel Na 1.2, is a high-risk gene associated with autism spectrum disorder (ASD) and has been linked to sensory hypersensitivity. Recent work indicates that Na 1.2 loss-of-function produces developmental and compartment specific alterations in neuronal signaling. However, how contributes to the maturation of subcortical auditory circuits that demand exceptional temporal precision remains unclear. METHODS: In this study, using haploinsufficient ( ) mice, we investigated the functional contribution of Na 1.2 to spike-generating mechanisms in the medial nucleus of the trapezoid body (MNTB), a fast inhibitory relay in the auditory brainstem organized along a medial-lateral tonotopic axis. RESULTS: In the pre-hearing period (P4-P6), haploinsufficiency reduced transient Na current amplitude and eliminated a delayed onset inward Na current component observed in a subset of wild type neurons, providing functional evidence for Na 1.2 dependent activity in developing MNTB neurons. Notably, Na 1.2 dependent deficits were tonotopically patterned. Lateral (low frequency) MNTB neurons exhibited the largest reductions in both transient Na current and persistent Na current, whereas medial neurons were comparatively spared in peak current magnitude. In current clamp, neurons displayed altered action potential kinetics during the pre-hearing window (slower and broader spikes), but repetitive firing during prolonged depolarizing steps was largely preserved, indicating that reduction impacts spike waveform maturation more than tonic spike count. After hearing onset, peak Na current amplitudes were comparable between genotypes (P14-P24), consistent with developmental reorganization of Na channel contributions. DISCUSSION: Together, these findings identify a pre-hearing, tonotopically biased role for in axon initial segment (AIS)-linked Na channel function and spike kinetics in the MNTB, providing a mechanistic framework for how may influence early auditory brainstem development relevant to sensory phenotypes in ASD.
From cellular heterogeneity to precision medicine: single-cell multi-omics in CNS disease research.
Liu T, Zhang Y, Hou W … +4 more , Hao H, Geng A, Zhao G, Zhang Y
Front Cell Neurosci · 2026 · PMID 42369569 · Full text
Single-cell sequencing and multi-omics technologies are revolutionizing research on central nervous system (CNS) diseases by enabling high-resolution analysis of cellular heterogeneity and molecular dynamics. Traditional...
Single-cell sequencing and multi-omics technologies are revolutionizing research on central nervous system (CNS) diseases by enabling high-resolution analysis of cellular heterogeneity and molecular dynamics. Traditional technologies (e.g., bulk sequencing, routine histology) often lack cellular resolution, fail to capture heterogeneity among individual cells, and struggle to reveal subtle molecular changes in early pathogenesis, limiting their ability to clarify complex CNS disease mechanisms and develop precise diagnostic tools. This review comprehensively summarizes the latest advances in single-cell multi-omics methodologies, including genomics, transcriptomics, proteomics, metabolomics, and spatial omics, and their applications in elucidating the pathogenesis, diagnosis, and treatment of common CNS disorders. Representative diseases such as ischemic stroke, Alzheimer's disease, Parkinson's disease, viral meningitis, bacterial meningitis, multiple sclerosis, autism spectrum disorder, and depression are used as examples to discuss the current status and future prospects of single-cell multi-omics technologies in CNS disease research. Currently, these technologies have enabled the identification of rare pathogenic cell subsets, the mapping of cell-specific molecular pathways, and the discovery of potential diagnostic biomarkers in several common CNS disorders, though their clinical translation is still hindered by technical costs and standardization issues. In the future, the integration of single-cell multi-omics with spatial transcriptomics, artificial intelligence, and clinical data is expected to further decode the complex pathogenesis of CNS disorders, accelerate the development of targeted therapies, and promote the shift toward personalized medicine in CNS disease management-aligning with translational goals of neuropsychopharmacology.
Mesenchymal stromal/stem cells for neurological disorders in humans: an evidence-mapped clinical review.
Lepski G, Arévalo A
Front Cell Neurosci · 2026 · PMID 42358489 · Full text
Mesenchymal stromal/stem cells (MSCs) have been tested clinically across a wide spectrum of neurological disorders, motivated by their immunomodulatory and trophic ("bystander") mechanisms rather than durable neural repl...
Mesenchymal stromal/stem cells (MSCs) have been tested clinically across a wide spectrum of neurological disorders, motivated by their immunomodulatory and trophic ("bystander") mechanisms rather than durable neural replacement. Here, we synthesize human prospective clinical trials that administered MSC products for neurological indications, prioritizing study design/goals, disease stage/severity, cell source/manufacturing, dose/route, detailed clinical assessments, quantified score changes, and adverse events (AEs). Across indications, trials frequently demonstrate feasibility and short-term safety, while efficacy signals are heterogeneous and strongly dependent on disease stage and endpoint selection criteria. The most methodologically rigorous signals with quantified motor outcomes include stereotactic intracerebral implantation of SB623 for chronic motor deficits after traumatic brain injury (TBI). In amyotrophic lateral sclerosis (ALS), randomized evidence supports safety and early slope-based signals in selected subgroups after intrathecal MSC regimens, but durable clinical benefit remains unproven. In hypoxic-ischemic encephalopathy (HIE), controlled data suggest functional improvements in small cohorts, and neonatal studies support feasibility adjunctive to hypothermia. We highlight design features most likely to de-risk efficacy interpretation: adequately powered randomized controlled trials, disease-stage stratification, prespecified clinically meaningful change thresholds, standardized rehabilitation co-interventions, and transparent AE adjudication.
A new framework for nicotinic receptor-targeted therapeutic strategies in psychiatric and neurodegenerative disorders.
Oudaha K, Causeret F, Koukouli F
Front Cell Neurosci · 2026 · PMID 42338505 · Full text
The nicotinic acetylcholine receptors (nAChRs) are key modulators of synaptic transmission and cognitive processing within the central nervous system. These ligand-gated channels, composed of various α and β subunits, me...
The nicotinic acetylcholine receptors (nAChRs) are key modulators of synaptic transmission and cognitive processing within the central nervous system. These ligand-gated channels, composed of various α and β subunits, mediate a plethora of neuronal functions including attention, memory and executive control. The current perspective article synthesizes recent advances on the contribution of pivotal nAChRs subtypes particularly α4β2, α7, and α5-containing receptors to cortical circuit function, highlighting their relevance in health and disease. In healthy brain, nAChRs regulate excitatory-inhibitory balance and enhance cognitive mechanisms in the prefrontal cortex (PFC) and hippocampus. Recent findings demonstrate that α5-containing receptors exhibit selective resistance to amyloid-β induced dysfunction, suggesting a neuroprotective role in Alzheimer's disease (AD). Integrating molecular, cellular, and behavioral evidence, we argue that receptor-subtype-specific modulation of distinct nAChRs subunits represents a promising therapeutic avenue for restoring network balance and cognitive function across neuropsychiatric and neurodegenerative disorders. We further discuss the role of nicotine in brain circuits and suggest that future research should prioritize precision pharmacology and genetic profiling to identify optimal therapeutic windows and mitigate the long-term consequences of nicotine exposure on developing neural circuits.
Plasticity, injury-induced reprogramming, and translational applications of Schwann cells in neural regeneration.
Zhu Y, Zhong J, Wang Z … +3 more , Gu X, Wang S, Li M
Front Cell Neurosci · 2026 · PMID 42338504 · Full text
Schwann cells (SCs), the predominant glial cell population in the peripheral nervous system (PNS), have undergone a paradigm shift from historically passive structural components of myelinated axons to active, multifunct...
Schwann cells (SCs), the predominant glial cell population in the peripheral nervous system (PNS), have undergone a paradigm shift from historically passive structural components of myelinated axons to active, multifunctional regulators of neural development, regeneration, and neuropathology. This review briefly outlines Schwann cell developmental origin as a biological backdrop, while centering on their inherent phenotypic plasticity and translational applications. Following peripheral nerve injury, SCs rapidly undergo context-dependent dedifferentiation and transcriptional reprogramming, acquiring a regenerative phenotype characterized by phagocytic activity, secretion of neurotrophic factors, and structural reorganization into Büngner bands. Notably, both endogenous and exogenously delivered SCs demonstrate capacity to migrate into lesioned central nervous system (CNS), including spinal cord injury sites, where they contribute to remyelination, modulation of glial scar formation, and partial restoration of electrophysiological connectivity and behavioral function. These attributes collectively establish SCs as phenotypically adaptable cellular mediators capable of facilitating neural repair across anatomically and functionally distinct compartments. To inform translational efforts, this review critically evaluates emerging strategies, including autologous cell transplantation and SC-derived exosomes, by appraising their mechanisms, limitations, and future perspectives. This review aims to deepen the mechanistic understanding of Schwann cell biology and provide a theoretical basis for the development of regenerative treatments for peripheral nerve injury and spinal cord injury.
How do signals propagate in neuronal compartments? Insights from the Poisson-Nernst Planck model.
Paragot P, Krell S, Guerrier C
Front Cell Neurosci · 2026 · PMID 42326840 · Full text
The emergence of novel experimental techniques such as dendritic patch-clamp recordings or genetically-encoded Ca2+-indicators have made the activity of the dendritic tree considerably more tractable, challenging the old...
The emergence of novel experimental techniques such as dendritic patch-clamp recordings or genetically-encoded Ca2+-indicators have made the activity of the dendritic tree considerably more tractable, challenging the old postulate that dendrites serve mainly to connect neurons and to convey information with no specific role in synaptic plasticity. Hence, how the dendritic tree transforms synaptic input into neuronal output and defines the relationships between active synapses is now a leading question in neuroscience. To understand the specific role of dendrites, dendritic spines and dendritic tree geometry in shaping neuronal signal, a crucial first step is to understand precisely voltage and ionic dynamics in such small neuronal compartments. For this purpose, we use the Poisson-Nernst-Planck (PNP) model, which is the recognized standard for modeling voltage dynamics and ionic electrodiffusion in electrolytes at the scale now reached by experimental techniques. This non-linear model presents significant challenges for both modeling and simulation due to its high concentration gradients and sensitivity to boundary conditions, making it difficult to simulate on complex geometries. We resolve these issues here by using a state-of-the-art finite volume method, the Discrete-Duality Finite Volume method, which we previously developed to simulate the PNP system of equations on various two-dimensional geometries representing neuronal compartments. Using this method, we investigate the propagation and attenuation of an ionic influx coming from a synapse near a dendritic branch bifurcation and at a dendritic spine, as well as signal invasion in the nearby branches and spines. By connecting these compartments to an ionic reservoir representing the dendritic shaft, we observe that the distance to the shaft strongly influences signal propagation. Notably, a spine positioned close to a large branch behaves as an isolated compartment, while a distant spine is susceptible to signal invasion. Our numerical results therefore suggest that the local geometry of the dendritic tree has a major influence on spine behavior. Consequently, this study proposes that signal integration rules would differ depending on the location of the spine on the dendritic tree. This means that modifications to neuronal structure and organization following activity are not limited to the spine morphology but depend on the entire dendritic tree architecture.
Editorial: From molecules to function: the world of mesencephalic trigeminal nucleus neurons in health and disease.
Bae YC, Toyoda H, Kang Y
Front Cell Neurosci · 2026 · PMID 42317586 · Full text
Abstract loading — click title to view on PubMed.
Peripheral biomarkers of neuronal damage in neuropsychiatric systemic lupus erythematosus (NPSLE).
Reyes-Mata MP, González-Palacios A, López-Llamas A … +4 more , Valle Y, Ortuño-Sahagún D, Marín-Rosales M, Palafox-Sánchez CA
Front Cell Neurosci · 2026 · PMID 42317585 · Full text
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with heterogeneous clinical presentations, including Neuropsychiatric SLE (NPSLE), which comprises a spectrum of central and peripheral nervous system m...
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with heterogeneous clinical presentations, including Neuropsychiatric SLE (NPSLE), which comprises a spectrum of central and peripheral nervous system manifestations attributable to immune-mediated neuronal and glial injury. Currently, diagnosing NPSLE is challenging due to the heterogeneous clinical manifestations and the lack of specific biomarkers. Breakthrough biomarkers are essential for improving diagnostic accuracy, prognostic assessment, and therapeutic monitoring in NPSLE. Serum biomarkers have been thoroughly examined, including inflammatory molecules such as cytokines, chemokines, and autoantibodies; however, these biomarkers are not brain-specific and have also been associated with other clinical domains of SLE. The present review focuses on neuronal and glial damage biomarkers in the context of NPSLE, highlighting their potential utility as diagnostic or prognostic biomarkers, while underscoring the need for further research in this area. Here, we discuss correlations between serum and cerebrospinal fluid (CSF) levels, supporting the use of serum as a minimally invasive surrogate for CNS assessment. Furthermore, findings on serum biomarkers of neurological damage were reviewed to explore their associations with clinical, demographic, and routine laboratory variables, which could provide insights into disease mechanisms. We identified potential biomarkers and highlighted important research gaps that may guide future investigations.
A comparative study of clinical efficacy, electrophysiological outcomes, and perioperative parameters between endoscopic carpal tunnel release and open carpal tunnel release for carpal tunnel syndrome.
Zhang Z, Liu Y, Yang H … +2 more , Song B, Shou K
Front Cell Neurosci · 2026 · PMID 42317584 · Full text
PURPOSE: To compare the clinical efficacy of endoscopic (ECTR) and open (OCTR) carpal tunnel release for carpal tunnel syndrome (CTS) and provide evidence-based surgical guidance. METHODS: A retrospective cohort study wa...
PURPOSE: To compare the clinical efficacy of endoscopic (ECTR) and open (OCTR) carpal tunnel release for carpal tunnel syndrome (CTS) and provide evidence-based surgical guidance. METHODS: A retrospective cohort study was conducted including 112 consecutive patients with CTS treated at our institution between January 2022 and December 2024. Based on the surgical approach, patients were assigned to an ECTR group or an OCTR group. Surgical selection was determined by patients' preference, cosmetic expectations, and the surgeon's technical assessment. Primary outcome measures were the Boston Carpal Tunnel Questionnaire Symptom Severity Score (BCTQ-SSS), Functional Status Score (BCTQ-FSS), and pain assessed by the Visual Analog Scale (VAS). Secondary outcome measures included median nerve electrophysiological indices [sensory nerve conduction velocity (SNCV), sensory nerve action potential (SNAP) amplitude, distal motor latency (DML), and compound muscle action potential (CMAP) amplitude], operative time, hospitalization cost, and postoperative complications. All outcomes were evaluated preoperatively and at the final follow-up (cutoff date: February 2026, with postoperative follow-up duration ranging from 13 to 48 months). RESULTS: Eighty-two eligible patients were followed up for a median of 34 months (13-48 months). Both groups showed significant improvements in VAS, BCTQ scores, and electrophysiological parameters versus baseline (all < 0.05), with no intergroup differences (all > 0.05). OCTR had significantly shorter operative time and lower cost (both < 0.001), and complication rates did not differ significantly ( > 0.05). CONCLUSION: ECTR and OCTR have comparable mid-term efficacy for CTS. OCTR is more cost-effective with shorter operative time, while ECTR's minimally invasive advantages need further confirmation. Surgical choice should be individualized based on patient preferences and institutional resources.
Neural stem cell-derived extracellular vesicles drive early neuroprotective and anti-apoptotic responses in spinal cord injury organotypic slices.
Sintakova K, Sprincl V, Arzhanov I … +3 more , Klassen R, Valihrach L, Romanyuk N
Front Cell Neurosci · 2026 · PMID 42317583 · Full text
INTRODUCTION: Spinal cord injury (SCI) is a devastating neurological condition with limited regenerative capacity. Stem cell-based approaches have emerged as promising strategies due to their neuroprotective and immunomo...
INTRODUCTION: Spinal cord injury (SCI) is a devastating neurological condition with limited regenerative capacity. Stem cell-based approaches have emerged as promising strategies due to their neuroprotective and immunomodulatory properties, largely mediated by small extracellular vesicles (sEVs) and their molecular cargo, including miRNAs. In this study, we aimed to evaluate the neuroprotective and anti-apoptotic potential of sEVs derived from SPC-01 and iMR-90 neural stem cell sources using an rat model of SCI. METHODS: sEVs were isolated from SPC-01 and iMR-90 culture media and characterized by MADLS and Western blot. Spinal cord slices (SCS) were used as an SCI model with three groups: control, SCI, and SCI treated with sEVs. Injury was induced at 18-20 days , followed by immediate sEV application. After 72 h, tissue samples were collected and analyzed to assess proteins associated with apoptosis, cytoskeletal integrity, and survival signaling pathways. RESULTS: SCI induced cytoskeletal disruption and increased apoptotic markers. sEV treatment attenuated these changes, reducing injury-associated proteins toward baseline levels. Both SPC-01- and iMR-90-derived sEVs showed neuroprotective effects. This was associated with modulation of key pathways, including decreased PTEN, increased STAT3 phosphorylation, and elevated Bcl-xL. Reduced Nogo-A and normalized RhoA levels further indicate attenuation of inhibitory signaling and improved cytoskeletal stability. Overall, sEVs promoted early neuroprotective responses and reduced pathology-associated protein expression in the SCI model. DISCUSSION: Neural stem cell-derived sEVs promote neuroprotection by modulating PTEN/STAT3 signaling, reducing apoptosis, and stabilizing cytoskeletal dynamics. Although limited to early injury responses in an model, these findings support sEVs as a promising cell-free therapeutic strategy for SCI.
Early life shifts in cortical inhibitory-excitatory balance underlies sensitive periods and skill development.
Taliaz D
Front Cell Neurosci · 2026 · PMID 42317582 · Full text
Early human development is characterized by sensitive periods which impact long-term cognitive and behavioral outcomes. While these windows of heightened plasticity are well documented, the cellular mechanisms that enabl...
Early human development is characterized by sensitive periods which impact long-term cognitive and behavioral outcomes. While these windows of heightened plasticity are well documented, the cellular mechanisms that enable and regulate them remain incompletely understood. In this conceptual article, I propose that early-life shifts in cortical inhibitory-excitatory balance, driven by prolonged neurogenesis, migration, and maturation of GABAergic interneurons, play a central role in opening, shaping, and closing sensitive periods and thereby guide skill development. Drawing on evidence from human and animal studies, I synthesize findings showing that inhibitory interneurons are integrated into cortical circuits well into postnatal life, where they regulate intrinsic and sensory-driven activity, sculpt synaptic connectivity, coordinate interactions with glial cells, and progressively refine network dynamics. The developmental strengthening of inhibition alters excitation-inhibition ratios, drives the transition from highly synchronous early activity to decorrelated and efficient adult-like firing patterns, and gates critical period plasticity across cortical regions. I argue that these inhibitory processes are not merely stabilizing but actively facilitate learning by suppressing non-relevant activity and enabling the emergence of specialized functional networks. This framework highlights fundamental differences between infant and adult learning mechanisms and suggests that individual variability in inhibitory circuit development may underlie differences in cognitive trajectories and vulnerability to neurodevelopmental disorders. Together, this synthesis positions early inhibitory interneuron development as a key mechanistic substrate linking sensitive periods to lifelong skill acquisition and behavioral individuality.
Editorial: Spatial and regional mapping of brain neural communication.
Paluh JL, Das D, Mukherjee A
Front Cell Neurosci · 2026 · PMID 42317581 · Full text
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Modulation of corneal sensory processing and pain responses by dry eye and corneal wounding.
Yaman E, Qu Y, Arpaia KC … +9 more , Elsaeidi F, Balakrishnan UL, He L, Skrehot H, Alam J, Chen R, Stepp MA, de Paiva CS, Pflugfelder SC
Front Cell Neurosci · 2026 · PMID 42311786 · Full text
BACKGROUND: Dry eye disease (DED) is a multifactorial disorder of the ocular surface in which tear film instability, epithelial barrier disruption, and neurosensory dysfunction contribute to symptom generation. Although...
BACKGROUND: Dry eye disease (DED) is a multifactorial disorder of the ocular surface in which tear film instability, epithelial barrier disruption, and neurosensory dysfunction contribute to symptom generation. Although several contributing factors have been identified, how different forms of ocular surface stress affect sensory pathways and behavioral responses remains unclear. PURPOSE: This study aimed to evaluate corneal barrier function, sensory responses, and pain-related behaviors across acute and chronic dry eye and corneal injury models, and to assess stimulus-specific responses associated with TRPV1 and TRPM8 mediated pathways. METHODS: Female C57BL/6 J wild type and Mmp9KO mice were evaluated in acute desiccating stress (DS), chronic [lacrimal gland excision (LGE) and aging], and corneal epithelial debridement models. Tear production, corneal barrier integrity, and mechanical and chemical sensitivity were assessed using established assays. Behavioral responses, including palpebral aperture height-width ratio (HWR), blink frequency, and pawing, were quantified following stimulation with capsaicin, hypertonic saline, and menthol. Human dry eye subjects were analyzed using video based measurements of HWR and blink frequency. RESULTS: Acute and chronic dry eye models and patients showed reduced palpebral aperture and decreased mechanical sensitivity. Sensitivity to CO₂ gas was unchanged, except in Mmp9KO. Capsaicin, hypertonic saline, and menthol reduced HWR in acute dry eye, with the greatest effect from capsaicin. Chronic dry eye showed reduced sensitivity to capsaicin and no change to hypertonic saline. Corneal debridement reduced mechanical sensitivity but increased responses to chemical stimulation. CONCLUSION: Reduced mechanical corneal sensitivity and palpebral aperture HWR represent consistent sensory phenotypes across dry eye models and patients, supporting translational relevance. Divergent responses to chemical stimuli between acute and chronic dry eye suggest neurosensory processing evolves with disease chronicity and engages distinct sensory pathways.
Neuregulin-1 promotes early regenerative and autophagic responses after ischemic stroke via spatial proteomics.
Noll JM, McGinley C, Augello CJ … +6 more , Kürüm E, Pan L, Pavenko A, Nam A, Ford BD, Ford GD
Front Cell Neurosci · 2026 · PMID 42311785 · Full text
Ischemic stroke remains a leading cause of death and long-term disability, yet effective treatments that promote recovery beyond the acute phase are lacking. Neuregulin-1 (NRG-1) has shown potent neuroprotective and anti...
Ischemic stroke remains a leading cause of death and long-term disability, yet effective treatments that promote recovery beyond the acute phase are lacking. Neuregulin-1 (NRG-1) has shown potent neuroprotective and anti-inflammatory properties in preclinical stroke models, with evidence of enhanced neuronal regeneration when administered after injury. To investigate the spatial mechanisms underlying its neuroregenerative therapeutic effects, we examined brain proteomic responses to post-ischemic NRG-1 treatment in mice using NanoString Digital Spatial Profiling (DSP). Adult C57BL/6 mice were subjected to photothrombotic middle cerebral artery occlusion (MCAO) and treated with NRG-1β (5 μg/kg/day) or vehicle at 24- and 48-h post-stroke. Brains were collected at 3 days post-ischemia for spatial proteomic analysis of 68 neural proteins across the ischemic core, peri-infarct tissue, and peri-infarct normal tissue (PiNT). While NRG-1 did not significantly alter overall neuronal death, it markedly reshaped the neuroregenerative milieu, upregulating myelin basic protein (MBP) and synaptophysin and attenuating inflammatory mediators (SPP1, P2RX7, and CD39). NRG-1 also enhanced expression of autophagy and mitophagy markers (ULK1, LC3B, ATG5, PINK1, and Park7), suggesting restoration of cellular clearance and mitochondrial quality control. Pathway and network analyses revealed activation of neuroregeneration, autophagy, and lysosomal biogenesis pathways, while suppressing neuroinflammatory signaling. These findings demonstrate that delayed NRG-1 therapy, even when initiated 24 h after stroke, induces early molecular programs that prime an anti-inflammatory and neuroregenerative environment. The results support further development of NRG-1 as a clinically translatable, multimodal therapy for extending the post-stroke treatment window and promoting functional recovery.
Acute hyperexcitability differentially affects hippocampal neurogenesis features and spatial memory.
López-Ibarra D, Aguilar-Arredondo A, Gaytan-Zeron V … +4 more , Hernández-Mercado K, Montiel T, Osorio-Gómez D, Zepeda A
Front Cell Neurosci · 2026 · PMID 42311784 · Full text
INTRODUCTION: Epileptic seizures induce aberrant adult hippocampal neurogenesis (AHN), yet how varying seizure intensities affect this process and associated memory functions remains unclear. METHODS: Here we administere...
INTRODUCTION: Epileptic seizures induce aberrant adult hippocampal neurogenesis (AHN), yet how varying seizure intensities affect this process and associated memory functions remains unclear. METHODS: Here we administered systemically a low (5 mg/kg) or a high (25 mg/kg) dose of kainic acid (KA) to induce acute hyperexcitability of differing severity in mice of both sexes (6 to 8 weeks-old) genetically labeled for Ascl1, which allowed to follow progenitor cells and their progeny in the dentate gyrus (DG). We recorded EEG, assessed spatial and contextual fear memory, and analyzed adult-born granule cells (abGCs) 32 days post-treatment. RESULTS: High-dose KA produced more severe and prolonged seizures, increased mature abGCs with altered laminar positioning, and elevated dendritic spine density, whereas low-dose KA induced presynaptic bouton enlargement. Both doses impaired spatial location recognition but spared contextual fear memory. DISCUSSION: These findings reveal that acute seizure severity differentially modulates morphological and synaptic features of abGCs and selectively disrupts hippocampal-dependent spatial memory, indicating that hyperexcitability exerts qualitative effects on neurogenesis and cognitive function.
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