Frontiers in Cellular Neuroscience最新文献

{"title":"From cellular regeneration toward functional integration: a 15-year bibliometric analysis of inner ear hair cell regeneration (2011-2025).","authors":"Xiaoyi Zhang, Lintao Tang, Dongmei Guan, Xinghong Liu, Hui Xie","doi":"10.3389/fncel.2026.1888383","DOIUrl":"10.3389/fncel.2026.1888383","url":null,"abstract":"<p><p>Sensorineural hearing loss, affecting over 1.5 billion people worldwide, results largely from irreversible damage to inner ear hair cells-specialized mechanosensory receptor cells that mammals cannot spontaneously regenerate. While recent advances in gene therapy and stem cell biology have raised hopes for biological repair, the rapid expansion of research has made it difficult to identify overarching trends, knowledge gaps, and translational bottlenecks. This study provides the first bibliometric analysis focusing on inner ear hair cell regeneration, covering 1,035 publications identified from the Web of Science Core Collection after systematic screening. To ensure the robustness of the findings and assess the sensitivity of the findings to database choice, we performed cross-database validation using Scopus and PubMed, which revealed high overlap rates (82.65% for PubMed and 75.76% for Scopus) and consistent patterns in the non-overlapping subset, suggesting that the primary WoSCC-based findings are not qualitatively altered by the inclusion of literature from other major databases. Using VOSviewer and CiteSpace, we analyzed publication trajectories, country/institution contributions, collaboration networks, and keyword dynamics. The results reveal a sustained increase in annual output, with the United States and China emerging as the two most productive and collaboratively central countries in the global research network. Keyword burst analysis shows a temporal shift from structural characterization (early 2010s) to signaling pathways (mid-late 2010s), and more recently to pathological mechanisms and protective strategies (late 2010s-present), including synaptopathy, transplantation, protection, ototoxicity, replacement, autophagy, and disease. VOSviewer co-occurrence analysis further reveals thematic clusters centered on hair cell regeneration and signaling, ototoxic injury and protection, and gene therapy and delivery, suggesting a field expanding from basic mechanisms toward translational research. These findings demonstrate that the field has diversified from a predominant emphasis on cellular regeneration toward broader attention to functional reconstruction of the hair cell-spiral ganglion neuron synapse. This transition underscores a growing emphasis on multi-target synaptic integration and highlights an unmet need for immune-compatible, subtype-specific gene delivery systems. Overall, this analysis, supplemented by cross-database consistency checks, provides a quantitative roadmap.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1888383"},"PeriodicalIF":4.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prefrontal cortex as a target of HIV-1 neurotoxicity: molecular mechanisms of viral protein-mediated neurodegeneration and executive dysfunction.","authors":"Erin S Honsa","doi":"10.3389/fncel.2026.1899622","DOIUrl":"10.3389/fncel.2026.1899622","url":null,"abstract":"<p><p>Despite the success of combined antiretroviral therapy (cART) in achieving peripheral viral suppression, HIV-associated neurocognitive disorder (HAND) remains a persistent challenge, affecting approximately 50% of people living with HIV. This review identifies the prefrontal cortex (PFC) as a primary target of HIV-1 neurotoxicity, as HIV-1 can directly infect the brain, and cART fails to eliminate the production of viral proteins from latent HIV-microglial reservoirs. The blood-brain barrier receives several hits from HIV-1 proteins, leading to a leaky and highly permeable barrier. Several proteins drive chronic neuroinflammation through inflammasome activation and pyroptosis, and ferroptosis in microglia. Glutamatergic dysregulation in the CNS results in increased neuron excitability and neurotoxicity. Also, overactive complement-mediated synaptic pruning and microglial senescence disrupt the intricate neural networks required for higher-order signaling. Neuroimaging and PFC dysfunction can be linked to specific HIV-1 proteins and their effects on the brain. Clinical symptoms of HAND directly reflect specialized PFC dysfunction. Deficits include impaired executive processes, which can present as lacking foresight for goal-directed actions, poor planning, and difficulty switching between tasks. Significant behavioral changes, including disinhibition, impaired moral reasoning, and increased risk-taking, can also be seen. Patients experience apathy, emotional blunting, and rapid mood shifts. Cognitive impairments include working memory loss, distractibility, and inappropriate memory linking. PFC disruptions can escalate into neuropsychiatric sequelae, driven by damaged dopamine and serotonin pathways. Defining these viral-mediated mechanisms will facilitate the development of pharmacological strategies that target several HIV-mediated neurotoxic pathways to prevent the debilitating characteristics of HAND.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1899622"},"PeriodicalIF":4.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The survival motor neuron protein: structure, functions, stability, and therapeutic targeting.","authors":"Bradley R Smith, Rachel Massalee, Mason Mayer, Brendan M Melvin, Arianna Valeri, Cecelia C Mangione, Barrington G Burnett","doi":"10.3389/fncel.2026.1894100","DOIUrl":"10.3389/fncel.2026.1894100","url":null,"abstract":"<p><p>The survival motor neuron (SMN) protein is an essential and highly versatile assembly factor that coordinates RNA metabolism and ribonucleoprotein (RNP) complex formation across multiple cellular compartments. Although SMN is required for the survival of virtually all cell types, its deficiency disproportionately affects <i>α</i>-motor neurons, causing their selective degeneration and giving rise to spinal muscular atrophy (SMA). Once viewed primarily as a motor neuron disease, SMA is now understood to be a multi-systemic disorder in which cell-intrinsic dysfunction extends to skeletal muscle, inflammatory glial cells, and metabolic organs. This review examines the regulatory mechanisms that control SMN protein stability, collectively termed proteostasis, with a focus on how post-translational modifications coordinate with the ubiquitin-proteasome system and the autophagy-lysosomal pathway to govern protein turnover and clearance. We also address the emerging concept of gene dosage sensitivity, including the underappreciated paradox that therapeutic SMN overexpression can be as harmful as deficiency, producing distinct toxicities in both neuromuscular and peripheral tissues. Finally, we highlight the need for next-generation combination therapies that integrate genetic modifiers, targeted degradation strategies, and post-translational regulators to maintain SMN levels within the narrow physiological range required for safety and efficacy.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1894100"},"PeriodicalIF":4.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Neural differentiation and neurorestorative effects of mesenchymal stem cells in brain disorders.","authors":"Ivana R Romano, Dirk M Hermann, Giuliana Mannino, Debora Lo Furno","doi":"10.3389/fncel.2026.1954548","DOIUrl":"10.3389/fncel.2026.1954548","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1954548"},"PeriodicalIF":4.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Molecular and cellular mechanisms underpinning adaptation and recovery after spinal cord injury.","authors":"Esther Giraldo, Victoria Moreno-Manzano, Guillem Paniagua-Soriano","doi":"10.3389/fncel.2026.1956734","DOIUrl":"https://doi.org/10.3389/fncel.2026.1956734","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1956734"},"PeriodicalIF":4.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Unraveling the long-term effects of COVID-19.","authors":"Romina Vuono, Kieren S J Allinson, Donato Zipeto, Nigel Temperton","doi":"10.3389/fncel.2026.1926660","DOIUrl":"https://doi.org/10.3389/fncel.2026.1926660","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1926660"},"PeriodicalIF":4.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultraviolet radiation and neurodegeneration: molecular mechanisms underlying dual neuroprotective and neurotoxic effects.","authors":"Shreya Praharaj, Eshika Chakraborty, Gayathri Mahalingam","doi":"10.3389/fncel.2026.1909393","DOIUrl":"10.3389/fncel.2026.1909393","url":null,"abstract":"<p><p>Ultraviolet radiation exhibits a complex, often contradictory link to neurodegeneration risk/progression, spanning clinically diagnosed diseases [Parkinson's Disease (PD), Alzheimer's Disease (AD), Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS)] or intermediate phenotypes (decreased neurogenesis, loss of hippocampal volume). The aim of this review is to highlight the dual impact of UV radiation by collecting and synthesizing experimental (preclinical and translational) evidence as well as epidemiological evidence. Current literature exhibits a clear dichotomy: while Vitamin D is capable of exerting a potent neuroprotective effect via anti-oxidant and anti-inflammatory pathways, chronic and intense UV radiation exposure actually hastens the progression or even drives neurodegeneration via a variety of mechanisms. UV radiation exerts its effects through various interconnected pathways: DNA damage pathways, ROS mediated pathways, vitamin D signaling and the skin-brain axis, which unifies both protective and degenerative effects of UV radiation. Owing to the increasing occurrence of neurodegenerative diseases in the general population, these pathways and mechanisms must be leveraged in future research to develop novel therapeutic and preventive strategies. Investigation of biomarkers linked to certain genetic and environmental factors that could provide a link to predisposition toward neurodegeneration and standardization of UV radiation dosimetry (exposure dose/duration) across experimental or pre-clinical studies must also be prioritized.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1909393"},"PeriodicalIF":4.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: From the mouth to the brain: exploring the link between periodontitis/peri-implantitis and neuroinflammation.","authors":"Gestter Willian Lattari Tessarin, Dirk M Hermann","doi":"10.3389/fncel.2026.1944333","DOIUrl":"10.3389/fncel.2026.1944333","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1944333"},"PeriodicalIF":4.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Swelling-induced calcium signaling in wild-type and <i>Mlc1</i>-null astrocytes: paradoxical effects of pharmacological TRPV4 and Piezo1 inhibition.","authors":"Quinty Bisseling, Vera Kuhnke, Maria S Brignone, Elena Ambrosini, Huibert D Mansvelder, Marjo S van der Knaap, Rogier Min","doi":"10.3389/fncel.2026.1908522","DOIUrl":"10.3389/fncel.2026.1908522","url":null,"abstract":"<p><strong>Introduction: </strong>Astrocytes play a crucial role in brain ion and water homeostasis and continuously adapt their volume in response to osmotic challenges. This process is disturbed in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC). Intracellular calcium signaling in response to cell swelling has been implicated in astrocytic volume regulation.</p><p><strong>Methods: </strong>We examined swelling-induced calcium signals in cultured astrocytes isolated from brains of wild-type and <i>Mlc1</i>-null mice, utilizing a microplate reader and Fura-2AM-based imaging.</p><p><strong>Results: </strong>We showed that wild-type astrocytes respond to hypotonic shocks with a robust calcium signal proportional to the magnitude of the shock. Pharmacological experiments indicated that these responses reflect a combination of intracellular store-mediated calcium release and channel-mediated calcium influx. <i>Mlc1</i>-null astrocytes showed an increased baseline calcium level and a slower calcium response to large hypotonic shocks. Unexpectedly, pharmacological inhibition of mechanosensitive cation channels with the TRPV4 antagonist HC-067047 and the mechanosensitive channel inhibitor GsMTx4 did not reduce swelling-induced calcium signals but instead led to a paradoxical increase in amplitude and speed of calcium signals in wild-type and <i>Mlc1</i>-null astrocytes, with differences in the magnitude of alteration between the two genotypes.</p><p><strong>Discussion: </strong>Together, our results suggest subtle alterations in calcium signaling that might affect the volume sensing machinery of <i>Mlc1</i>-null astrocytes, conforming with earlier studies that show mistuning of volume-regulated ion channels in MLC. The observed paradoxical effects are consistent with a role for TRPV4- and GsMTx4-sensitive pathways in setting basal responsiveness of astrocytes to osmotic stress, and argue against TRPV4 or Piezo1 being the main direct calcium entry routes during swelling. Overall, our findings highlight the complexity of astrocytic volume regulation in response to hypotonicity.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1908522"},"PeriodicalIF":4.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in responses to panicogen CO₂ inhalation and the role of microglial acid-sensor TDAG8 in female mice.","authors":"Shawn Lam, Pragnya Sai Priya Munisetti, Rebecca Ahlbrand, Renu Sah, Katherine M J McMurray","doi":"10.3389/fncel.2026.1865360","DOIUrl":"10.3389/fncel.2026.1865360","url":null,"abstract":"<p><p>Prior work found microglial acid-sensor T-cell death-associated gene 8 (TDAG8) mediates panic-relevant responses to interoceptive stressor CO₂ inhalation in male mice. Yet panic disorder is more common in women and panic attack symptoms vary in men and women. Here, we investigated sex differences in CO₂-evoked behavioral and physiological responses in mice. We also investigated the role of TDAG8 in regulating CO₂ inhalation-evoked fear-relevant behaviors and hyperventilation, as well as microglial morphology following CO₂ inhalation in female mice. We found CO₂ inhalation evoked greater fear-relevant behaviors and hyperventilation in female compared to male mice. Contrary to prior findings in males, we found TDAG8 deletion did not affect fear-relevant defensive responses to CO₂ inhalation in females. However, TDAG8 deletion significantly attenuated CO₂-evoked hyperventilation in females. Previous work in male mice showed CO₂ inhalation induces morphological indicators of microglial activation within circumventricular organ the subfornical organ (SFO) in a TDAG8-dependent manner. Consistent with males, TDAG8 deletion in females attenuated morphological indicators of microglial activation following CO₂ inhalation within the SFO, but not within another TDAG8-expressing circumventricular organ, the organ vasculosum of the lamina terminalis (OVLT). This suggests a divergence in the role of TDAG8 in mediating behavioral versus physiological responses to panicogen CO₂ inhalation, though effects on SFO microglia are consistent. Together these data highlight important sex differences in behavioral and physiological responses to panicogen, CO₂ inhalation. They also highlight the need to consider phenotypic differences when exploring molecular mechanisms and circuitry driving panic-relevant outcomes in males and females.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1865360"},"PeriodicalIF":4.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}