Frontiers in Cellular Neuroscience最新文献

Astrocytes are the most abundant glial cells in the central nervous system. They detect neuronal activity through Ca²⁺ signals and thereby regulate synaptic plasticity, integrate neuronal information, and maintain extracellular homeostasis. Growing evidence indicates that aberrant astrocytic Ca²⁺ 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 Ca²⁺ signaling, with the aim of improving understanding of astrocyte function and providing new perspectives and rationale for therapeutic strategies targeting related diseases.

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.

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 (NO₂), ozone (O₃), 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.

[This corrects the article DOI: 10.3389/fncel.2025.1681891.].

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.

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.

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of highly persistent organofluorine compounds, and extensively used in industrial and consumer application. Their environmental ubiquity and bioaccumulation in humans have raised concerns about potential health impacts, particularly on neurodevelopment. This mini-review synthesizes epidemiological and experimental research published between 2020 and 2025 examining prenatal PFAS exposure and neurodevelopmental outcomes in children. Prospective birth cohort studies from Europe, North America, and Asia report subtle but statistically significant associations between higher maternal PFAS levels and a range of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), cognitive delays (e.g., reduced IQ, language impairments), and behavioral dysregulation. Mechanistic investigations reveal that PFAS can cross the placenta, alter maternal-fetal thyroid and sex-steroid hormone homeostasis, activate inflammatory pathways (e.g., AIM2 inflammasome), disrupt neurotransmitter systems (notably dopaminergic and GABAergic signaling), modulate fetal metabolomic profiles, and induce durable epigenetic modifications. Key methodological challenges include heterogeneity of PFAS mixtures, reliance on single-time-point exposure assessments, variable confounder control (e.g., socioeconomic status, maternal IQ, nutrition, breastfeeding), limited follow-up into later childhood or adolescence, and sparse data on emerging short-chain PFAS analogs. To strengthen causal inference and inform public health interventions, future research should employ longitudinal designs with repeated biomonitoring, standardized neuropsychological assessments, advanced mixture-modeling approaches, comprehensive confounder adjustment, inclusion of vulnerable populations, and focused evaluation of replacement PFAS. Coordinated efforts bridging epidemiology, mechanistic science, and regulatory policy are essential to mitigate PFAS exposure and safeguard neurodevelopmental health in future generations.

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 (n = 20) were analysed and compared to age-and sex-matched healthy controls (n = 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.

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 _ir channels and then distributed among neighboring astrocytes via gap junctions. Here, we tested the effect of blocking gap junctions and K _ir channels, both independently and simultaneously, on field excitability of cortical slices in response to a stimulation train. Independently blocking either gap junctions or K _ir 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 _ir 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 _ir 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 _ir block alone suggests that adaptive mechanisms may be recruited upon genetically induced astrocyte decoupling. We conclude that K⁺ buffering via K _ir 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.

[This corrects the article DOI: 10.3389/fncel.2025.1590493.].