Lacaille H, Lebayle E, Corneo B
… +2 more, Vacher CM, Penn AA
Front Cell Neurosci
· 2025 · PMID 41480491
·
Full text
Preterm birth substantially elevates the risk of neurological and cognitive disorders. Recent evidence suggests that the abrupt loss of placental support, particularly the cessation of neurotrophic and neuroprotective ho...Preterm birth substantially elevates the risk of neurological and cognitive disorders. Recent evidence suggests that the abrupt loss of placental support, particularly the cessation of neurotrophic and neuroprotective hormones, alters neurodevelopmental trajectories and may contribute to neurodevelopmental risk associated with prematurity. Our study investigates how the placental steroid hormone, allopregnanolone (ALLO), affects cerebral cortex development using human cortical organoid models. Our findings reveal that while ALLO exposure produces modest effects on overall cortical development, its withdrawal specifically disrupts GABAergic but not glutamatergic neuronal development. These results demonstrate that placental hormones, including ALLO, may target specific neuronal populations critical for cortical function, identifying potential therapeutic interventions following placental loss in human preterm neonates.
Haustein MD, Deymier C, Schlienger S
… +9 more, Lexcellent-Bissler L, Mawet J, Gutknecht E, Thenoz L, Brazauskas P, Renault B, Brun S, Winistörfer S, Portmann T
Front Cell Neurosci
· 2025 · PMID 41472709
·
Full text
Neuroscience drug discovery is challenged by the brain's structural and cell-type complexity, which is difficult to model in cellular systems compatible with high-throughput screening methods. Calcium oscillation assays,...Neuroscience drug discovery is challenged by the brain's structural and cell-type complexity, which is difficult to model in cellular systems compatible with high-throughput screening methods. Calcium oscillation assays, that harness neurons' intrinsic capability to develop functional neural networks in cell culture, are currently the closest cellular models with a relevant functional endpoint to model human neuronal circuitry in a dish. Here we further developed this useful assay towards scalable drug discovery applications. We show the importance of defined neuron-to-astrocyte ratios for optimal cellular distribution and surface adherence in HTS-compatible cell culture vessels and how the cell type ratios affect network firing patterns. Increasing the neuron density resulted in decreased network spike frequencies, but increased network spike amplitudes. We identified DAPT, a molecule previously shown to promote neuronal maturation and synapse formation, as a negative regulator of astrocyte viability. Furthermore, inclusion of GABAergic neurons in the cocultures increased the network spike frequency while reducing network spike amplitudes. The GABA receptor antagonist bicuculline did not affect network spike frequency, but increased network spike amplitudes. In order to access local field activity in an automated and scalable calcium imaging environment, we developed a pixel-based analysis for plate reader data. This method revealed that the effect of GABAergic neurons and bicuculline was restricted to local field calcium activity that coincided with synchronized network spikes. Our observations are consistent with previous findings suggesting that the presence of GABAergic neurons decreases synchronization and network spike participation of local neuronal activity, thus potentially echoing aspects of GABA action , and dysregulation thereof in pathological conditions.
Front Cell Neurosci
· 2025 · PMID 41472708
·
Full text
BACKGROUND: Alzheimer's disease (AD) has long been associated with hallmark protein aggregates, yet increasing evidence suggests immune involvement may contribute to its progression. Prior studies have found increased T...BACKGROUND: Alzheimer's disease (AD) has long been associated with hallmark protein aggregates, yet increasing evidence suggests immune involvement may contribute to its progression. Prior studies have found increased T cell presence in AD brain tissue, raising the possibility of neuroimmune crosstalk. METHODS: We used single-nucleus RNA sequencing data from the Religious Orders Study and Memory and Aging Project (ROSMAP), the largest available postmortem AD cohort, to investigate T cell dynamics in prefrontal cortex (PFC) and hippocampus. RESULTS: Contrary to prior findings, we observed no significant increase in T cell frequency in individuals with pathologically confirmed AD in either region. We replicated these findings in dorsolateral PFC (DLPFC) using the Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Notably, although we confirmed a prior finding of T cell expansion in middle temporal gyrus (MTG), the strength of this association was affected by donor age. Additionally, we detected no change in gene expression in T cells in the brain parenchyma from individuals with AD. IMPACT: These results suggest that T cell enrichment in AD may be regionally restricted and not as widespread as previously assumed. Our findings underscore the importance of brain region selection, analytical approach, and dataset composition in interpreting immune cell dynamics in neurodegenerative disease.
Front Cell Neurosci
· 2025 · PMID 41472707
·
Full text
OBJECTIVE: To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) on extrapyramidal neural network of Wilson disease (WD). METHODS: 27 6-month-old toxic milk mice (TX mice, WD animal model) and 15 C57 m...OBJECTIVE: To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) on extrapyramidal neural network of Wilson disease (WD). METHODS: 27 6-month-old toxic milk mice (TX mice, WD animal model) and 15 C57 mice were selected. Corrected phase (CP) value on susceptibility weighted imaging (SWI), fractional anisotropy (FA) on diffusion tensor imaging (DTI) were performed. The volume of fiber connections was determined. BMSCs was transplanted though tail vein injection (1 × 10, 0.5 mL). The myelin basic protein (MBP), amyloid precursor protein (-APP), nitric oxide (NO), glutathione (GSH) and interleukin (IL-1β) were determined at 1, 2, 4 and 8 weeks after transplantation. RESULTS: The CP value of TX mice increased at 4 ( = 0.029) and 8 weeks ( = 0.037) after transplantation. FA values ( = 0.026, 0.020, 0.037) and the volume of neural fibers ( = 0.016, 0.023, 0.018) increased at 2, 4 and 8 weeks after transplantation. The pathological indexes of demyelination (MBP) and axon injury (-APP) improved after BMSCs transplantation. The brain copper content decreased at 4 and 8 weeks after transplantation ( = 0.024, 0.038). The indexes of oxidative stress (NO and GSH) and inflammation (IL-1β) of TX mice were improved after transplantation. CONCLUSION: BMSCs can ameliorate WD extrapyramidal neural network injury. The mechanism may be related to reducing copper deposition and alleviating oxidative stress and inflammatory response.
Front Cell Neurosci
· 2025 · PMID 41438969
·
Full text
Neurodegenerative diseases are frequently accompanied by inflammatory responses and alterations in lipid metabolism, both of which are believed to negatively affect neural regeneration in mammals. In addition to immune c...Neurodegenerative diseases are frequently accompanied by inflammatory responses and alterations in lipid metabolism, both of which are believed to negatively affect neural regeneration in mammals. In addition to immune cells, glial cells such as astrocytes and microglia contribute significantly to these inflammatory processes, and it is now recognized that lipid droplet accumulation and cholesterol metabolism are dysregulated in these glial cells. Consequently, recent studies have examined inflammation and lipid metabolism from the standpoint of glial cell function; however, effective therapeutic strategies remain unestablished. By contrast, in zebrafish, a teleost species, robust neural regeneration occurs within a short period after injury to the telencephalon or spinal cord. In this review, we aimed to identify candidate functional factors by comparing mouse and zebrafish disease models and to explore molecules with potential therapeutic relevance for mammalian neurological disorders.
Front Cell Neurosci
· 2025 · PMID 41427445
·
Full text
Microglia can selectively phagocytose live neurons during normal development and also in response to stress, injury or disease by recognizing phagocytic cues to target cells for elimination. In the developing retina at e...Microglia can selectively phagocytose live neurons during normal development and also in response to stress, injury or disease by recognizing phagocytic cues to target cells for elimination. In the developing retina at embryonic stages we previously found that microglia refine retinal ganglion cell (RGC) numbers by targeting non-apoptotic newborn RGCs for phagocytosis, utilizing complement receptor 3 (CR3) to recognize and eliminate RGCs. Here, we investigate additional phagocytic mechanisms and cues that microglia utilize to clear a subset of viable RGCs. Our findings indicate that both Mer tyrosine kinase (Mertk) and CR3 are required for clearance of a subpopulation of embryonic RGCs. In Mertk/CR3 double knockouts, we show that C1q-tagged RGCs accumulate and excess RGCs persist indicating failure of normal clearance by microglia. We also show that microglia target RGCs that have phosphorylated c-JUN (p-cJUN) expression, suggesting stress pathway activation. RGCs with p-cJUN expression also accumulate in Mertk/CR3 double knockout retinas, but this appears to resolve by P0, suggesting this is a transient stress state exhibited by a subset of RGCs that remain viable. By depleting microglia we establish that microglia are not required for p-cJUN induction in RGCs but show that they are the sole source of complement protein C1q, which marks these cells for elimination. Altogether the data suggests that a subset of stressed RGCs are recognized by local microglia that tag them with opsonins for removal using specific recognition receptors.
Yi C, Luo C, Zhao J
… +10 more, Roubeix C, Lechner J, Penalva R, Yang N, Liu J, Wang Q, Chakravarthy U, Sennlaub F, Chen M, Xu H
Front Cell Neurosci
· 2025 · PMID 41427444
·
Full text
PURPOSE: To investigate the impact of low-dose, long-term aspirin use on neovascular age-related macular degeneration (nAMD). METHODS: Adult C57BL/6J or Thbs-1 mice were treated with daily aspirin (1.25 mg/kg) for 8 week...PURPOSE: To investigate the impact of low-dose, long-term aspirin use on neovascular age-related macular degeneration (nAMD). METHODS: Adult C57BL/6J or Thbs-1 mice were treated with daily aspirin (1.25 mg/kg) for 8 weeks before being subjected to laser-induced choroidal neovascularization (CNV). The animals were left for 7-10 days with continued aspirin use before the eyes were collected for further investigations. Bone marrow-derived macrophages (BMDMs) and primary retinal pigment epithelial (RPE) cells were treated with different concentrations of aspirin (1, 10, 100 μM) for two days before being subjected to LPS+IFNγ for 16 h. The expression of cytokine genes was evaluated by qRT-PCR. The concentrations of thrombospondin-1 (TSP-1) were measured by ELISA. RESULTS: Aspirin treatment did not affect circulating immune cell profiles in normal mice but significantly increased CD11b cells in laser-induced CNV mice. The treatment significantly increased the severity of laser-induced CNV and reduced serum levels of TSP-1. aspirin treatment upregulated and , down-regulated mRNA expression, and reduced TSP-1 production in LPS+IFNγ-treated M1 BMDMs but not RPE cells. Thbs-1 mice developed severe laser-induced CNV, which was not affected by aspirin intervention. nAMD patients had significantly lower serum levels of TSP-1 than healthy controls, although no significant difference was found between nAMD patients with and without aspirin use. CONCLUSION: Low-dose long-term aspirin use promoted the severity of laser-induced CNV by down-regulating TSP-1. Lower serum levels of TSP-1 may be a risk factor for nAMD. The long-term ocular safety of aspirin should be validated in prospective cohorts.
Kocakusak H, Kök AB, Ozturk B
… +2 more, Karacicek B, Genc S
Front Cell Neurosci
· 2025 · PMID 41415912
·
Full text
tRNA-derived small RNAs (tsRNAs) have recently gained attention as important regulatory non-coding RNAs (ncRNAs). Among these, tRNA-derived fragments (tRFs) constitute a distinct and well-defined subset. These small mole...tRNA-derived small RNAs (tsRNAs) have recently gained attention as important regulatory non-coding RNAs (ncRNAs). Among these, tRNA-derived fragments (tRFs) constitute a distinct and well-defined subset. These small molecules play essential roles in maintaining cellular homeostasis and have been increasingly implicated in disease pathogenesis. This comprehensive review specifically concentrates on tRFs, takes a closer look at their diverse mechanisms of action and their impact on key cellular processes. Specific focus is placed on their functions within the central nervous system (CNS) and their involvement in the molecular pathways driving neurological diseases and neurodevelopmental disorders. Besides their pathological roles, the review covers fundamental aspects of tRFs, including their biogenesis, classification, and structural features. It also describes latest methods for tRFs detection, prediction, and validation. Overall, the review points out the ongoing need for research in this area, especially when it comes to applying these findings clinically. Importantly, it highlights their potential as useful biomarkers and even targets for treatment in neurological diseases.
Czyrska J, Ziętek MM, Bernat A
… +1 more, Sampino S
Front Cell Neurosci
· 2025 · PMID 41393782
·
Full text
The corpus callosum (CC) is the largest interhemispheric commissure in the eutherian brain, enabling inter-hemispheric sensory integration and higher-order cognitive functions. Historically viewed through a neuron- and a...The corpus callosum (CC) is the largest interhemispheric commissure in the eutherian brain, enabling inter-hemispheric sensory integration and higher-order cognitive functions. Historically viewed through a neuron- and axon-centric lens, extensive research has established that glial cells (astrocytes, oligodendrocytes, and microglia) are essential regulators of CC ontogenesis. Astrocytic guidepost cells sculpt midline architecture and secrete axonal guidance cues; oligodendrocytes drive callosal axonal maturation and myelination; and microglia regulate their fasciculation and pruning, myelination patterns, and synaptic refinement. In addition to these cell-specific roles, coordinated bidirectional signaling between neurons and glia ensures that axon targeting, maturation, and interhemispheric integration proceed in a precisely orchestrated manner. Disruptions to these glial functions are implicated in congenital and developmental brain pathologies, including malformations and CC agenesis. This review integrates molecular, developmental, and translational insights to provide a comprehensive, mechanistic understanding of glial contributions to CC development and how their dysfunction shapes pathology.
Front Cell Neurosci
· 2025 · PMID 41393781
·
Full text
Neuroglia, comprising three cell types (astrocytes, oligodendrocytes and microglia), interact with neurons and extracellular components in brain physiology. Astroglia, having as main function the control of homeostasis,...Neuroglia, comprising three cell types (astrocytes, oligodendrocytes and microglia), interact with neurons and extracellular components in brain physiology. Astroglia, having as main function the control of homeostasis, modulate dynamic processes in the nervous system, including mental functions; they are crucially involved in all neurological, psychiatric and degenerative disorders and diseases. How to change the century-old neuron-centered paradigm used to explain experimental phenomena in the clinical domain? This is the question addressed in this paper. I review a new explanatory paradigm based on an "endogenous feedback" between astroglial and neuronal networks: neuronal bioelectricity generates Local Field Potentials, which are synchronized, generating a dynamic field that impacts on a multi-ion population, releasing 'shuttles' that induce amplitude-modulated spatiotemporal patterns on astroglial 'calcium waves'. The 'calcium wave' activates other signaling processes, as the release of ions in the "synaptic cradle," to control the temporal dynamics of spike trains of the post-synaptic neuron and metabolic processes determining behavioral and endocrine responses. The "endogenous feedback" theoretical hypothesis can be tested by means of a combination of new techniques of visualization and analysis of amplitude-modulated spatiotemporal patterns present in astroglia , registers of behavioral patterns and subjective reports (in the case of alert persons under invasive brain surgery procedures), addressing the issue of how astroglial 'calcium waves' modulate neuronal dynamics, mediating brain processing of stimuli to produce adaptive responses.
Chen Y, Ye Y, Jia J
… +3 more, Long B, Dou T, Yan X
Front Cell Neurosci
· 2025 · PMID 41383745
·
Full text
Astrocytes are the most abundant glial cells in the central nervous system. They detect neuronal activity through Ca signals and thereby regulate synaptic plasticity, integrate neuronal information, and maintain extracel...Astrocytes are the most abundant glial cells in the central nervous system. They detect neuronal activity through Ca signals and thereby regulate synaptic plasticity, integrate neuronal information, and maintain extracellular homeostasis. Growing evidence indicates that aberrant astrocytic Ca signaling is an important pathological factor in the onset and progression of many neurological disorders. In this review, we systematically summarize the sources, classifications, detection methods, and functional significance of astrocyte Ca signaling, with the aim of improving understanding of astrocyte function and providing new perspectives and rationale for therapeutic strategies targeting related diseases.
Mann-Nüttel R, Armbruster M, Mandal S
… +1 more, Forsythe P
Front Cell Neurosci
· 2025 · PMID 41376717
·
Full text
The essential role of the lungs in gas exchange necessitates exposure to possible threats from a dynamic external environment. To protect life-critical functions the airways contain multiple systems that monitor the inha...The essential role of the lungs in gas exchange necessitates exposure to possible threats from a dynamic external environment. To protect life-critical functions the airways contain multiple systems that monitor the inhaled environment and elicit appropriate defensive responses. As such the airways represent a key sensory surface with multiple signaling pathways to the brain. Despite the presence of rich and diverse bacterial communities in both upper and lower airways, the respiratory tract has been relatively overlooked compared to the gut regarding its potential as an interface between microbes and the central nervous system. This review draws attention to the respiratory system, specifically the nasal cavity and lungs, and the evidence supporting a microbiota-airway-brain axis. We highlight the olfactory system and the role of the lungs as a sensory organ, monitoring the inhaled environment, as clear examples of airway-brain communication and identify how these communication pathways can be engaged by microbes. We also outline the relationship between the airways and mental health and present the case that the nasal and lung microbiota should be considered alongside that of the gut as potential influencers of brain function, mood, and behavior.
Abarca-Castro EA, Reyes-Lagos JJ, Guzmán Ramos K
… +6 more, Montiel-Castro AJ, Arano-Varela H, Mayer-Villa PA, Aguilar-Toalá JE, Montesillo-Cedillo JL, Talavera-Peña AK
Front Cell Neurosci
· 2025 · PMID 41376716
·
Full text
We offer an integrative perspective on how the air-pollution exposome shapes fetal development during the first 1,000 days and reverberates across mental health and behavior. Pregnant individuals and young children are d...We offer an integrative perspective on how the air-pollution exposome shapes fetal development during the first 1,000 days and reverberates across mental health and behavior. Pregnant individuals and young children are disproportionately exposed to particulate matter (PM2.5), nitrogen dioxide (NO), ozone (O), and volatile organic compounds (VOCs) with social disadvantage amplifying risk. We bridge exposure to biology through three conduits. First, the placenta acts as a sensor and recorder, transducing signals that alter growth, immune tone, and neuroendocrine programming. Second, fetal autonomic control-captured by beat-to-beat fetal heart rate variability (fHRV) offers a relevant biomarker of neurodevelopmental integrity; the absence of direct ambient-pollution-fHRV studies is a pressing gap. Third, maternal immune activation, oxidative and endoplasmic reticulum (ER) stress, and disrupted morphogenesis reshape developing circuits, changes now traceable in utero by advanced fetal MRI. These pathways fit a developmental-programming frame: epigenetic remodeling, gene-environment interplay, endocrine-disrupting co-exposures, and gut-microbiome shifts create durable susceptibility. Clinically, the result is structural and functional brain alterations and child phenotypes spanning attention, executive control, affecting regulation, and learning, with clear pediatric and educational implications. We propose an exposome-based research agenda coupling high-resolution exposure assessment with placental molecular profiling, fetal/neonatal autonomic biomarkers (including fHRV), fetal/child neuroimaging, and longitudinal microbiome readouts in harmonized cohorts. In parallel, multisectoral actions-clean air urban design, targeted protection of pregnancy and early childhood, chemical regulation, and risk communication-should narrow exposure inequities while trials test biomarker-guided prevention. Aligning placental biology, autonomic metrics, and exposome science may transform risk stratification and safeguard the developing brain.
Ryan KM, O'Rourke A, Sheridan C
… +5 more, Balcells Quintana M, Moran B, Fletcher JM, McLoughlin DM, Harkin A
Front Cell Neurosci
· 2025 · PMID 41356500
·
Full text
INTRODUCTION: Immunological changes are implicated in the pathophysiology of depression. We aimed to assess phenotype and frequency of immune cell subtypes, including an assessment of regulatory T cells and production of...INTRODUCTION: Immunological changes are implicated in the pathophysiology of depression. We aimed to assess phenotype and frequency of immune cell subtypes, including an assessment of regulatory T cells and production of cytokines by T cell subsets following stimulation. METHODS: Using a flow cytometric analysis, peripheral blood samples obtained from medicated patients with depression ( = 20) were analysed and compared to age-and sex-matched healthy controls ( = 21), and in patients with depression after electroconvulsive therapy (ECT) in a real-world clinical setting. Depression severity was assessed using the Hamilton Depression Rating Scale (HAM-D24). RESULTS: A reduction in the frequencies of CD19+ B cells and IL-17+ CD8 T cells was evident in depressed patients compared to healthy controls. For a subgroup of depressed patients assessed pre- versus post-ECT, there was no change in phenotype, frequency or function of immune cell subtypes within 72 hours of completing treatment. Further exploratory analyses found that baseline CD16-CD14+ classical monocyte frequency correlated with change in HAM-D24 score post-ECT, indicating that a higher frequency of classical monocytes at baseline is associated with greater symptom improvement after treatment. A reduced number of CCR7-CD45RO+ effector memory T cells was also found to be associated with an improvement in symptoms post-ECT. DISCUSSION: Overall, these results demonstrate that flow cytometry is useful for immune profiling to identify altered adaptive immune features in depression and potential biomarkers of ECT response. In particular, changes in classical monocytes and effector memory T cells were associated with treatment response in patients with unipolar depression.
Front Cell Neurosci
· 2025 · PMID 41356499
·
Full text
The discovery of neuronal activity-dependent calcium transients in astrocytes has driven the conceptualization of these cells as computational units in the nervous system. Tripartite synapses, consisting of pre- and post...The discovery of neuronal activity-dependent calcium transients in astrocytes has driven the conceptualization of these cells as computational units in the nervous system. Tripartite synapses, consisting of pre- and postsynaptic terminals along with an adjacent astrocyte, enable astrocytes to communicate with and shape the activity of local synapses. In the hippocampus, astrocytes encode and modulate information through a variety of mechanisms, including tuning the gating of single synapses in their domains, coordinating oscillatory activity across neuronal circuits through astrocytic networks, and providing a foundation for long-term memory formation through intracellular signaling and metabolic coupling. The bidirectional and complementary activities of astrocytes and neurons can be situated in a framework that positions astrocytes as integrators and modulators of neuronal activity, both locally and globally. In this review, we focus on hippocampal astrocytes and discuss recent progress toward understanding astrocytic function in concert with neurons to mediate circuit function and, ultimately, behavior.
Bojovic D, Dagostin A, Sullivan SJ
… +3 more, Emery B, von Gersdorff H, Mishra A
Front Cell Neurosci
· 2025 · PMID 41356497
·
Full text
Astrocytes are connected in a functional syncytium via gap junctions, which contribute to the maintenance of extracellular K homeostasis. The prevailing hypothesis is that K released during neuronal firing is taken up by...Astrocytes are connected in a functional syncytium via gap junctions, which contribute to the maintenance of extracellular K homeostasis. The prevailing hypothesis is that K released during neuronal firing is taken up by astrocytes via K channels and then distributed among neighboring astrocytes via gap junctions. Here, we tested the effect of blocking gap junctions and K channels, both independently and simultaneously, on field excitability of cortical slices in response to a stimulation train. Independently blocking either gap junctions or K channels increased the amplitude of the first fEPSC (field excitatory post-synaptic current) response, followed by suppression of both fiber volley (pre-synaptic action potentials) and fEPSCs during sustained stimulation. Surprisingly, simultaneous block of both gap junctions and K channels enhanced the suppression of neuronal activity, resulting in a ∼75% decrease in fiber volley amplitude in the first response, followed by a fast and strong suppression of fEPSCs during sustained stimulation. Genetic depletion of astrocyte gap junctions showed a reduction but not complete loss of Cx43, indicating partial syncytial decoupling, and, accordingly, had a weaker but similar effect on neuronal excitability as blocking gap junctions. Pharmacological K block in mice with reduced gap junction coupling suppressed sustained firing of the fiber volley but not fEPSCs. That this effect was milder than K block alone suggests that adaptive mechanisms may be recruited upon genetically induced astrocyte decoupling. We conclude that K buffering via K and gap junctions in astrocytes together play a critical role in maintaining neuronal excitability, particularly during sustained activity, but that other mechanisms can be recruited to perform this function in their absence.
Front Cell Neurosci
· 2025 · PMID 41356496
·
Full text
Neural stem cells (NSCs) hold significant potential in neural regenerative medicine, yet research faces multiple challenges such as cellular heterogeneity, unclear microenvironment interactions, and low clinical translat...Neural stem cells (NSCs) hold significant potential in neural regenerative medicine, yet research faces multiple challenges such as cellular heterogeneity, unclear microenvironment interactions, and low clinical translation efficiency. In recent years, the rapid development of artificial intelligence (AI) technologies has provided new ideas and tools to address these issues. This paper reviews the current applications of AI in fundamental NSCs research, including intelligent identification, deep learning-driven subtype analysis, spatial microenvironment deconstruction, and dynamic analysis of neural differentiation. Additionally, we discuss several key AI technologies not yet applied to NSCs research, such as generative adversarial networks, graph neural networks, and self-supervised learning, as well as their potential applications in cell classification, interaction network analysis, and morphological feature extraction. Although AI technologies show great promise in NSCs research, challenges remain regarding data quality, model robustness, and interpretability. Therefore, future research should focus on establishing high-quality standardized multimodal data platforms and integrating biological knowledge to enhance model interpretability, thereby deepening the understanding of NSCs biological characteristics and differentiation mechanisms and advancing personalized therapies.