Cellular and Molecular Neurobiology最新文献

{"title":"Activation of the Reverse Cholesterol Transport Pathway: A Strategy to Ameliorate Lipid Metabolic Dyshomeostasis in the Microenvironment Following Spinal Cord Injury.","authors":"Xiaoxin Wang, Guina Tan, Ru Feng, Min Ni, Feng Gao, Jianjun Li","doi":"10.1007/s10571-026-01754-2","DOIUrl":"10.1007/s10571-026-01754-2","url":null,"abstract":"<p><p>Spinal cord injury (SCI) causes massive release of myelin‑derived lipids, driving macrophage‑to‑foam‑cell transformation that sustains inflammation and impedes repair. Although reverse cholesterol transport (RCT) mediates lipid efflux, its functional dynamics within the SCI microenvironment remain unclear. Using a mouse T10 contusion model, we examined key RCT components (ABCA1, ABCG1, and APOE) by qRT‑PCR, Western blot, and immunofluorescence. We also evaluated the LXR agonist AZ876 for its capacity to modulate RCT and promote functional recovery. We observed a pronounced imbalance in RCT after SCI. ABCA1 and APOE were persistently upregulated, but ABCA1 localized predominantly to astrocytes rather than macrophages. Notably, ABCG1 protein levels declined progressively despite increased mRNA expression, indicating a post‑transcriptional bottleneck that favors foam‑cell accumulation. AZ876 activated the LXR/RXR axis and induced long‑term transcriptomic remodeling of lipid metabolism. Early AZ876 treatment increased ABCA1 and partially restored ABCG1 protein expression, markedly reducing Oil Red O-positive foam‑cell accumulation at the lesion site. These microenvironmental improvements were associated with decreased TNF‑α levels and enhanced locomotor recovery, as evidenced by improved BMS scores and open‑field performance. The lipid-rich environment after spinal cord injury rapidly activates the initial steps of RCT, but a pronounced post-transcriptional suppression of ABCG1 impedes downstream RCT processes. Although the LXR agonist AZ876 partially overcomes this bottleneck and improves neurological outcomes, it fails to fully restore ABCG1 protein levels, indicating that transcriptional activation alone is insufficient. Future strategies should target the mechanisms of ABCG1 protein instability to fully correct lipid metabolic dysregulation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual CCR2/CCR5 Antagonism with Cenicriviroc Alleviates Nerve Injury-Induced Hypersensitivity and Prevents Morphine Tolerancevia Modulation of Neuroimmune Signaling.","authors":"Anna Piotrowska, Joanna Starnowska-Sokół, Katarzyna Ciapała, Justyna Barut, Katarzyna Pawlik, Agata Ciechanowska, Klaudia Kwiatkowski, Grzegorz Kreiner, Joanna Mika","doi":"10.1007/s10571-026-01761-3","DOIUrl":"10.1007/s10571-026-01761-3","url":null,"abstract":"<p><p>Mounting evidence implicates that chemokine receptors type 2 and 5 play a pivotal role in neuropathic pain. Here, we report for the first time that cenicriviroc, a dual CCR2/CCR5 antagonist, exerts strong, long-lasting, and morphine-potentiating effects in a mouse model of chronic constriction injury (CCI) to the sciatic nerve. The analgesic effect of cenicriviroc was comparable to that of morphine in the initial phase of neuropathy (Day 3) and, rewardingly, superior to the effect of morphine on Days 8 and 16 of twice-daily intraperitoneal administration. Moreover, on Day 16, tolerance to the analgesic effect of morphine was less pronounced in the group that received cenicriviroc before every morphine injection. Immunofluorescence analysis confirmed that CCR2 colocalizes with microglia/macrophages. Luminex analyses revealed time-dependent CCI-induced spinal increases in several kinases (p38, ERK, JNK, Akt), transcription factors (NF-κB, STAT3), and cytokines (IL-10, IL-1β, TNFα, CCL2/3/5). No less importantly, there was a pronounced elevation of pronociceptive mediators (TNFα, IL-1β, CCL2/3/4/5, pERK, and pNF-κB) following prolonged morphine administration over 16 days; all these factors can potentially contribute to the emergence of tolerance and tactile hypersensitivity. In contrast to morphine, cenicriviroc on Day 3 increased the level of antinociceptive IL-10, while decreasing pERK. Furthermore, on Day 8, cenicriviroc increased the level of Akt/STAT3, and decreased pp38/pERK and pronociceptive CCL2/3/5. The obtained results indicate that simultaneous targeting of CCR2/5 by cenicriviroc may have great potential for neuropathic pain therapies, especially since the drug is already in clinical trials for other conditions.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and Prognostic Value of Epigenetic Markers in Neurological Diseases. A Narrative Review.","authors":"Olga Grodzka, Justyna Wołos, Małgorzata Kupc, Sara Ahmadova, Ceren Eyileten, Izabela Domitrz","doi":"10.1007/s10571-026-01766-y","DOIUrl":"10.1007/s10571-026-01766-y","url":null,"abstract":"<p><p>Neurological disorders are a leading cause of disability and death, yet sensitive and specific biomarkers remain limited. Epigenetic modifications link genetic background with environmental influences and may improve diagnosis, prognosis, and treatment stratification. The study aimed to summarise the current knowledge on epigenetics in neurological diseases, primarily focusing on their diagnostic value. We performed a narrative review with elements of systematic methodology. PubMed was searched up to November 21, 2025, using broad neurology and epigenetics terms followed by disease-specific queries. Sixty-five original studies on epigenetic markers with diagnostic or prognostic utility in neurological diseases were included. Across neurological disorders, multiple disease-associated epigenetic signatures have been reported. In neurodegenerative diseases, deoxyribonucleic acid (DNA) methylation patterns, histone modifications, and non-coding ribonucleic acid (RNA) profiles discriminate patients from controls and correlate with disease stage and clinical outcomes. In multiple sclerosis, methylation changes in genes involved in disease pathogenesis and characteristic microRNAs may distinguish relapsing from progressive forms and relate to disability. In ischemic stroke and transient ischemic attack, epigenetic alterations in vascular, metabolic, circadian, and inflammatory pathways, together with non-coding RNAs and extracellular vesicle signatures, are associated with stroke risk, severity, and outcome. Evidence in epilepsy, migraine, myasthenia gravis, dystrophies, and leukodystrophies suggests additional disease-specific epigenetic candidates. Epigenetic biomarkers across DNA methylation, histone modifications, and non-coding RNAs hold substantial potential to enhance precision neurology, from early diagnosis to prognostic stratification and therapy guidance. However, current evidence is heterogeneous and often based on small cohorts and variable methodologies. Large, longitudinal studies with standardised protocols are required before routine clinical implementation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application Mechanisms and Clinical Prospects of Brain-Computer Interface Technology in Radiation-Induced Brain Injury.","authors":"Ruijun Xu, Xueqian Huang, Zhanlin Chen, Hussein Ali Mohamed, Xuyu He, Feiyang Lu, Yusen Ou, Ge Li, Kunyi Zhang","doi":"10.1007/s10571-026-01758-y","DOIUrl":"10.1007/s10571-026-01758-y","url":null,"abstract":"<p><p>Radiation-induced brain injury (RIBI) is a common complication of radiotherapy that leads to neurological symptoms, significantly impairing patients' daily functioning and long-term rehabilitation. Consequently, the development of effective therapeutic strategies has received considerable attention. As an emerging approach in the management of neurological disorders, brain-computer interface (BCI) technology shows substantial potential for both the assessment and treatment of RIBI. This review synthesizes evidence retrieved from electronic databases and examines RIBI from the perspectives of its mechanisms and clinical manifestations. Current findings suggest that BCI technology holds promise for several applications in RIBI, including early diagnosis, mitigation of neuroinflammation, alleviation of associated symptoms, and prediction and management of complications. The implementation of BCI is likely to play a significant role in early assessment and treatment processes for RIBI. Furthermore, with ongoing technological advancements, the development of next-generation BCI is expected to enable more targeted treatment that address additional pathological mechanisms of RIBI, thereby progressively improving the quality of life for affected patients.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Plasma T-LAK cell-originated protein kinase Owned the Potential for Predicting Favorable Outcomes in Acute Ischemic Stroke Patients.","authors":"Lingzhi Li, Ziping Han, Tong Shen, Zhenhong Yang, Junfen Fan, Rongliang Wang, Yangmin Zheng, Haiping Zhao, Qingfeng Ma, Yumin Luo","doi":"10.1007/s10571-026-01765-z","DOIUrl":"10.1007/s10571-026-01765-z","url":null,"abstract":"<p><p>T-lymphokine-activated killer-cell-originated protein kinase (TOPK), was widely overexpressed in various malignant tumors, and played critical roles in their growth, differentiation and metastasis. However, its levels and potential clinical significance in acute ischemic stroke (AIS) was unknown. We detected the plasma TOPK protein level and mRNA level of neutrophilic TOPK in AIS patients using ELISA and RT-PCR, and analyzed their association with functional outcomes statistically. Among 330 patients with AIS, plasma TOPK concentrations differed significantly between patients present with excellent outcomes or not at 3 months. Plasma TOPK ≥ 69.95 pg/mL independently predicted excellent functional outcomes. In the subgroup of patients received rt-PA treatment, patients with TOPK ≥ 69.95 pg/ml also predicted excellent functional outcomes. Addition of plasma TOPK to clinical predictors for excellent outcomes post AIS as well as outcomes after rt-PA treatment improved their reclassification and discrimination. Although TOPK mRNA levels were significantly elevated in the neutrophils of AIS patients, no significant predictive value was observed for excellent outcomes. Conclusively, higher plasma TOPK levels (especially TOPK ≥ 69.95 pg/ml) might emerge as a prognostic indicator for the 3-month excellent functional outcomes post AIS and possessed predictive value in identifying patients with 3-month excellent functional outcomes after rt-PA treatment.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Sphingosine 1-phosphate Modulators on Central Remyelination: A Systematic Review of Animal Models.","authors":"Harley Vu, Nelson George, Junhua Xiao","doi":"10.1007/s10571-026-01748-0","DOIUrl":"10.1007/s10571-026-01748-0","url":null,"abstract":"<p><p>Promoting remyelination is a key therapeutic goal in demyelinating diseases such as multiple sclerosis (MS), yet effective strategies remain limited. Sphingosine-1-phosphate (S1P), a ubiquitous bioactive lipid, has emerged as a key therapeutic target in MS due to its dual roles in immune regulation and neuroprotection; however, the therapeutic efficacy of current S1P-based therapies in remyelination remains unclear. This systematic review evaluated in vivo studies up to July 2025, in accordance with PRISMA guidelines, to assess the efficacy of S1P modulators on remyelination in mammalian models of demyelination. A comprehensive search across three databases identified 24 eligible studies that investigated S1P receptor (S1PR) modulation in both acute and chronic models of demyelination, with or without immune-mediated components. Fingolimod was the most extensively studied compound (16 studies). Of the 18 studies assessing demyelination outcomes, S1P modulation consistently attenuated myelin loss and oligodendrocyte depletion. In contrast, remyelination outcomes were inconsistent: among 15 studies assessing repair, most reported no significant enhancement. While fingolimod showed limited evidence on remyelination, more promising effects were observed with selective S1PR1/5 modulators such as siponimod and ponesimod. Overall, current evidence supports a model in which S1P modulators act primarily through S1PR1-mediated immunomodulation and S1PR5-associated oligodendroglial protection, preserving oligodendrocyte lineage cells rather than driving terminal differentiation or de novo remyelination. Several compounds displayed bell-shaped dose-response patterns, highlighting the importance of dosing and treatment paradigms. Collectively, these findings indicate S1PR-based therapies primarily limit demyelination, with limited evidence of remyelination, emphasising the need for more efficacious S1P modulators to improve MS outcomes.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of Neurocan in the Prefrontal Cortex Impairs Temporal Order Recognition, Cognitive Flexibility and Perisomatic GABAergic Innervation.","authors":"David Baidoe-Ansah, Hector Carceller, Hadi Mirzapourdelavar, Marta Pérez-Rando, Luisa Strackeljan, Borja Garcia-Vazquez, Constanze Seidenbecher, Rahul Kaushik, Juan Nacher, Alexander Dityatev","doi":"10.1007/s10571-026-01762-2","DOIUrl":"10.1007/s10571-026-01762-2","url":null,"abstract":"<p><p>The condensed form of the neural extracellular matrix (ECM), known as perineuronal nets (PNNs), is predominantly associated with parvalbumin-expressing (PV+) interneurons in the cortex and hippocampus. PNNs are enriched in lecticans, including neurocan (Ncan). Genetic variation in the human Ncan gene has been linked to alterations in hippocampus-dependent memory, structural differences in the prefrontal cortex (PFC), and increased risk for schizophrenia and bipolar disorder. However, the specific contribution of Ncan to PFC-dependent cognitive functions and synaptic organization remains incompletely understood. Here, we investigated the consequences of region-specific reduction of Ncan in the infralimbic cortex of mice, a region considered homologous to the dorsomedial part of the human medial PFC. Using intracortical adeno-associated virus delivery of shRNA targeting Ncan, we examined PNN-associated markers, synaptic organization, and PFC-dependent behaviors. Ncan knockdown was associated with reduced Wisteria floribunda agglutinin (WFA) labeling of PNNs surrounding PV+ interneurons, suggesting alterations in PNN composition. Behaviorally, mice with reduced Ncan expression exhibited mild but consistent impairments in medial PFC-dependent temporal order recognition memory and in aspects of reversal spatial learning in a labyrinth task. At the cellular level, immunohistochemical analyses revealed a reduction in markers associated with perisomatic GABAergic innervation of PV+ interneurons, together with an increase in the density of vGLUT1-immunopositive puncta in the surrounding neuropil. These structural changes were not observed in constitutive Ncan knockout mice, suggesting the presence of compensatory mechanisms in this model. Together, our findings highlight a functional role of Ncan in supporting perisomatic GABAergic innervation, temporal order recognition memory and cognitive flexibility, important cognitive resources impaired in neuropsychiatric disorders.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"46 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Sensory Neuropathies Through Neurotrophin-Based Approaches.","authors":"Veronica Mohamed Hizam, Di Prisco Stefania, Anna Pisani, Boccella Serena, Brandolini Laura, Claudio Grassi, Fabiola Paciello, Anna Rita Fetoni","doi":"10.1007/s10571-026-01756-0","DOIUrl":"10.1007/s10571-026-01756-0","url":null,"abstract":"<p><p>Neurotrophins, including NGF, BDNF, and NT-3, are crucial regulators of neuronal survival, synaptic plasticity, and regeneration in sensory systems. Emerging evidence suggests that neurotrophin signaling may represent a common biological axis underlying both sensory neuron vulnerability and repair across auditory, visual, and olfactory systems. This review examines the roles of neurotrophins in maintaining neuronal integrity, promoting synaptic repair, and facilitating functional recovery in sensory pathways. We delved into the molecular mechanisms by which neurotrophins influence neuronal survival and plasticity, with a particular focus on cochlear synaptopathy, optic neuropathy, and olfactory dysfunction. Additionally, we compared neurotrophin-based therapies to emerging approaches, such as gene therapy, small molecules, and cell-based treatments, emphasizing their potential to complement and enhance existing strategies. Despite their therapeutic promise, several challenges persist in translating neurotrophin therapies to clinical practice, including issues related to delivery efficiency and pharmacokinetics. Overall, neurotrophin-based interventions, especially when integrated with complementary regenerative approaches, may offer an effective strategy for restoring sensory function and modifying disease progression, paving the way for future clinical applications.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Level Light Therapy in Postherpetic Neuralgia: A Review of Mechanistic Insights and Clinical Implications.","authors":"Yu-Chen Ma, Yu-Chieh Chiang, Sebastian Yu","doi":"10.1007/s10571-026-01763-1","DOIUrl":"10.1007/s10571-026-01763-1","url":null,"abstract":"<p><p>Known as the most prevailing complication of herpes zoster (HZ), postherpetic neuralgia (PHN) can lead to long-term skin discomfort. Current medications for PHN remain suboptimal with incomplete relief and potential side effects. Low-level light therapy (LLLT) has been increasingly explored as a non-invasive modality for treating PHN, but the mechanistic basis and clinical implications have not been synthesized in a translational framework. In this review, we explore the pathophysiological mechanisms of PHN and the biological mechanisms of LLLT, integrating current mechanistic insights with available clinical evidence. We summarize the experimental and clinical literature evaluating LLLT for PHN and related neuropathic pain models, mainly focusing on mechanisms across peripheral tissues, dorsal root ganglia, and neuro-immune aspects, as we evaluate therapeutic parameters and outcomes from available clinical studies. Current evidence suggests that PHN is associated with dorsal root ganglion (DRG) inflammation, peripheral cutaneous neuroinflammation, loss of cutaneous innervation, and ion channel dysregulation. These changes comprehensively lead to hyperexcitable neurons with a lower sensory threshold. Across neuropathic pain models, LLLT elevates mechanical and thermal pain thresholds, attenuates inflammatory cytokine signaling, and promotes an immune cell phenotype shift toward an anti-inflammatory profile including M1-to-M2 macrophage polarization. LLLT also stabilizes membrane excitability by restoring Na⁺/K⁺-ATPase activity and modulating calcium dynamics, while supporting peripheral nerve repair via axonal regeneration. Clinically, administering LLLT to patients with PHN resulted in significant pain reduction, and early intervention may also reduce its incidence. By integrating experimental and clinical research, LLLT serves as a promising approach for PHN owing to its efficacy for anti-inflammation, neuronal regeneration and ion modulation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin II Receptor Signaling in the Hypothalamic-Pituitary-Adrenal Axis and Spleen After Spinal Cord Injury Depends on the Sympathetic Innervation Integrity.","authors":"Erika Kellerova, Jana Snopkova, Erika Hvozdikova, Jaroslav Pavel","doi":"10.1007/s10571-026-01760-4","DOIUrl":"10.1007/s10571-026-01760-4","url":null,"abstract":"<p><p>Spinal cord injury (SCI) disrupts the integrated neuroendocrine network linking the hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin-aldosterone system, and sympathetic nervous system, resulting in endocrine and immune dysfunction. However, the effects of SCI on angiotensin II receptor signaling remain unclear. This study investigated temporal and lesion-dependent changes in angiotensin II type 1 (AT₁) and type 2 (AT₂) receptor expression following SCI in rats. Low-thoracic SCI (Th9 compression, 40 g/15 min) was evaluated over 28 days, while acute responses to partial (Th9) versus near-complete (Th1) sympathoadrenal denervation were compared. Receptor expression was assessed in the hypothalamic paraventricular nucleus, pituitary, adrenal gland, and spleen, and correlated with hormonal and morphological alterations. Surgical stress alone activated systemic angiotensin II signaling. Low-thoracic SCI induced time- and tissue-specific changes in angiotensin receptor expression independent of circulating angiotensin II levels, indicating adaptive remodeling of HPA axis sensitivity. SCI caused transient adrenal enlargement, zona fasciculata hypertrophy, dysregulated HPA axis activity, angiotensin II-independent aldosterone production, and altered catecholamine secretion. Splenic AT₁ receptor expression showed early upregulation followed by compensatory downregulation, consistent with dynamic neuroimmune modulation. In contrast, high-thoracic SCI markedly reduced receptor expression across central and peripheral HPA axis components and the spleen, accompanied by decreased corticotropin-releasing hormone, aldosterone, and norepinephrine, stable adrenocorticotropic hormone, and elevated corticosterone and epinephrine. These findings demonstrate that the extent of sympathetic disruption critically determines neuroendocrine-immune responses after SCI and identify sympathetic innervation as a key regulator of angiotensin receptor balance and stress-axis homeostasis following spinal cord trauma.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}