Current Neuropharmacology最新文献

{"title":"Demyelination in Vascular Dementia: Focus on Oligodendrocytes, Microglia, and Their Interaction.","authors":"Ying Liu, Jiaming Li, Yang Zhao, Yuxiao Zheng, Jialin Cheng, Chuxin Zhang, Xin Lan, Jinhua Han, Jiahui Gao, Bomin Zhang, Sicheng Feng, Yixin Wang, Zilin Ren, Qingguo Wang, Fafeng Cheng, Changxiang Li, Xueqian Wang","doi":"10.2174/011570159X445971260216112740","DOIUrl":"https://doi.org/10.2174/011570159X445971260216112740","url":null,"abstract":"<p><p>Vascular dementia (VaD), a primary cognitive disorder caused by cerebrovascular pathology, features significant white matter damage from chronic cerebral hypoperfusion strongly correlated with cognitive decline. Myelin integrity disruption represents a core pathological foundation in VaD, with dysfunctional oligodendrocytes (OLs) and microglia (MG) forming a critical pathogenic nexus. OLs govern myelin formation and maintenance while MGs modulate myelination through cerebral microenvironment regulation. In the central nervous system, precise communication and synergistic interaction between cells are the basis for maintaining homeostasis and cognitive function. The complement system, cytokine network, and extracellular vesicles together form its core communication axis. The complement system is at the forefront of the rapid innate immune response, cytokines dynamically regulate the initiation and resolution of inflammation, as carriers of functional molecules between cells, extracellular vesicles target and deliver information of bioactive molecules, upgrading intercellular communication to an active and programmed network regulation system. The three work together to maintain the homeostasis of the neural microenvironment. Their dysregulation can lead to uncontrolled neuroinflammation and tissue damage, which is the core pathological link in diseases such as VaD. This review examines the interplay between OLs and MG in VaD demyelination, detailing their complex communication networks via the complement system (including C1q, C3, C5 fragments), key cytokines (TNF-α, IL-1β, IL-4, IL-10), and extracellular vesicle signaling. Notably, these pathways exhibit bidirectionality: moderate activation promotes repair mechanisms, whereas excessive responses exacerbate injury. Future research should elucidate the spatiotemporal dynamics of OLs-MG interactions and identify precise therapeutic targets to restore cellular equilibrium, thereby informing novel VaD intervention strategies.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Prolactin Predicts High-Frequency Repetitive Transcranial Magnetic Stimulation Response on Immediate Memory in Schizophrenia.","authors":"Anle Pan, Qiang Hu, Jing Yao, Dianming Zhu, Meihong Xiu","doi":"10.2174/011570159X442103260206084946","DOIUrl":"https://doi.org/10.2174/011570159X442103260206084946","url":null,"abstract":"<p><strong>Introduction: </strong>The therapeutic effects of rTMS may be mediated, at least in part, by the neuroendocrine mechanism. The present study was designed to investigate whether baseline hormone concentrations predict clinical response to rTMS in schizophrenia.</p><p><strong>Methods: </strong>This is a secondary analysis of 84 patients with schizophrenia enrolled in a previously published randomized, sham-controlled trial. All participants completed 30 sessions of highfrequency rTMS applied to the left dorsolateral prefrontal cortex. We assessed cognitive functioning before and after prefrontal rTMS intervention. Blood hormone levels were determined in the hospital laboratory.</p><p><strong>Results: </strong>High-frequency rTMS showed a significant improvement in immediate memory relative to sham. At baseline, there was no difference in hormone levels between the real and sham rTMS groups. However, baseline prolactin (PRL) levels were positively associated with rTMS efficacy in the real rTMS group, and patients with higher baseline PRL levels showed greater improvement in immediate memory than those with lower levels. Linear regression analysis adjusting for age, symptom severity, baseline immediate memory, antipsychotic dosage, and types revealed that PRL at baseline was a predictor of the response to rTMS in patients with schizophrenia. No other hormone predicted cognitive outcome.</p><p><strong>Discussion: </strong>Our findings suggest a potential role for PRL levels in predicting rTMS efficacy, particularly in improving immediate memory in patients with schizophrenia, providing further evidence for the individualisation of future rTMS treatments.</p><p><strong>Conclusions: </strong>Our findings suggest a potential role for PRL levels in predicting rTMS efficacy, particularly in improving immediate memory in patients with sc.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurovascular Coupling Dysfunction: An Early Indicator of Brain Injury in Asymptomatic Moyamoya Disease.","authors":"Rui Hu, Jinhao Lyu, Ziqi Liu, Qi Duan, Chaobang Xie, Xiaokuan Hao, Caohui Duan, Song Wang, Xiangbing Bian, Jianxing Hu, Rong Wang, Lian Duan, Xin Lou","doi":"10.2174/011570159X440563260226104506","DOIUrl":"https://doi.org/10.2174/011570159X440563260226104506","url":null,"abstract":"<p><p>Neurovascular Coupling Dysfunction: An Early Indicator of Brain Injury in Asymptomatic Moyamoya Disease.</p><p><strong>Introduction: </strong>This study investigated structural and functional impairments in asymptomatic Moyamoya Disease (MMD) patients with normal signals to support early interventions. It focused on Neurovascular Coupling (NVC), cerebral perfusion, neural activity, and white matter microstructure in adults with unilateral and bilateral MMD, examining their impact on cognitive function.</p><p><strong>Methods: </strong>119 asymptomatic MMD adults (57 unilateral, 62 bilateral) underwent MRI assessments. Data on demographics, clinical, and neuropsychological parameters were collected. Comparative analyses of Cerebral Blood Flow (CBF), white matter diffusion, neuronal activity, and NVC were conducted, with Spearman correlation analyses assessing the link between imaging differences and cognitive function, adjusting for multiple comparisons.</p><p><strong>Results: </strong>The study identified that patients with bilateral asymptomatic MMD had lower NVC across two coupling modes (P = 0.004/0.049) and fractional anisotropy within two clusters (P = 0.028/0.039), alongside higher radial diffusivity in three clusters (P = 0.046) compared to those with unilateral involvement. While neuronal activity differed, CBF changes were not significant. NVC demonstrated a positive correlation with fractional anisotropy (P = 0.005) and was negatively related to radial diffusivity across two clusters (P = 0.025/0.018). Furthermore, both fractional anisotropy (P = 0.031) and NVC were positively associated with cognitive performance (P = 0.003).</p><p><strong>Discussion: </strong>This study shows that in asymptomatic MMD patients with normal signals, bilateral vascular involvement leads to more severe NVC impairments, despite similar CBF levels. This condition may worsen white matter damage and increase the risk of cognitive decline and adverse outcomes as the disease progresses. Early detection of NVC dysfunction could indicate a higher risk of future clinical issues and guide decisions on vascular reconstruction surgery. These findings suggest that NVC is an earlier indicator of brain dysfunction than traditional CBF measures in asymptomatic MMD patients.</p><p><strong>Conclusion: </strong>Bilateral asymptomatic MMD is associated with greater NVC impairment, possibly worsening microstructural damage and cognitive decline, suggesting a basis for targeted interventions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Harmonious Dance: A Narrative Review on Psychedelics and Music in Therapeutic Settings.","authors":"Hongshuang Wang, Xiaobing Li, Feng Yu, Xiaohui Wang","doi":"10.2174/011570159X442471260422110855","DOIUrl":"https://doi.org/10.2174/011570159X442471260422110855","url":null,"abstract":"<p><p>The integration of psychedelics and music in therapeutic settings is gaining recognition for its potential to enhance mental health outcomes. This review synthesizes current evidence on the neurobiological mechanisms underlying this synergy, focusing on receptor-level pathways (e.g., 5-HT2A receptor agonism, BDNF-TrkB signaling) and neural circuit dynamics (e.g., default mode network desynchronization, thalamo-cortical connectivity) that mediate psychedelic action and mu-sic-induced emotional processing. By examining how music, acting as a \"hidden therapist,\" ampli-fies the emotional and cognitive effects of psychedelics, we elucidate the mechanistic interplay that fosters deep psychological insights and emotional healing. Several key areas have been addressed, such as the exploration of dynamic brain activity in realistic music environments, the micro-neural mechanisms underlying basic musical elements, and the development of quantitative techniques for music therapy aimed at improving sleep quality and alleviating symptoms of anxiety and depression. Psychedelics increase neural plasticity and downregulate the default mode network, allowing music to guide emotional processing and facilitate profound therapeutic breakthroughs. The synergy be-tween music and psychedelics shows promise in treating conditions such as depression, Post-Traumatic Stress Disorder (PTSD), and addiction. The scientific contributions of this review include providing an integrated mechanistic framework for understanding psychedelic-music interactions and identifying key neurobiological targets for future therapeutic optimization. Future research should focus on optimizing therapeutic protocols and understanding the neurobiological mecha-nisms underlying this powerful combination to ensure its safe and effective integration into main-stream mental health care.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association between Ferroptosis and Glycolysis Following Subarachnoid Hemorrhage.","authors":"Ziyi Zhou, Xin Zhang","doi":"10.2174/011570159X471060260414115133","DOIUrl":"https://doi.org/10.2174/011570159X471060260414115133","url":null,"abstract":"<p><strong>Introduction: </strong>Subarachnoid hemorrhage (SAH) is a brain disorder. Ferroptosis is a recently discovered type of regulated cell death. Glycolysis is a key energy-metabolism pathway in the brain, and disruptions in balance are thought to be at the origin of early brain injury. It is recent studies have shown that there are complex links between ferroptotic and glycolytic pathway and it is possible that the interaction can cause the resulting SAH-related brain injury; however, it is not clear what the precise molecular origin is.</p><p><strong>Methods: </strong>This review summarizes the roles of ferroptosis and glycolysis in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) in the recent period, focusing on their mutual regulation and the impact on brain cell function or survival.</p><p><strong>Results: </strong>Recent results have shown how ferroptosis triggers neuronal apoptosis via iron overload and lipid peroxidation, while glycolytic metabolism also regulates cellular energy supply and the role of the antioxidant defense system. Ferroptosis, together with glycolysis, regulation of cellular energy metabolism, and expression of inflammatory factors, affects the survival and death of neurons and promotes the pathological process of EBI.</p><p><strong>Discussion: </strong>From the three dimensions of time, space, and cell type, we can formulate a comprehensive treatment strategy to jointly regulate ferroptosis and glycolysis, and dynamically monitor the early brain injury after subarachnoid hemorrhage.</p><p><strong>Conclusion: </strong>The analysis provides a theoretical foundation and research directions for elucidating the pathological mechanisms of post-SAH brain injury and developing targeted therapeutic strategies.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Model of Paclitaxel-Induced Peripheral Neuropathy Produces a Clinically Relevant Phenotype in Mice.","authors":"Laura R Osborn, Mary Grace Bishop, Kayleigh A Rodriguez, Dakota M Redling, Elizabeth A Duplechain, Kimberly E Stephens","doi":"10.2174/011570159X394711250909101152","DOIUrl":"10.2174/011570159X394711250909101152","url":null,"abstract":"<p><strong>Introduction: </strong>One of the most common adverse side effects of chemotherapeutics is chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel, a highly effective chemotherapeutic, is associated with a high incidence of paclitaxel-induced peripheral neuropathy (PIPN) that persists for over a year in 64% of patients and worsens with increasing cumulative paclitaxel dose. Patients experiencing PIPN may reduce the dosage of chemotherapy or halt treatment due to pain. Current preclinical models have improved our understanding of PIPN but have been ineffective in generating translational therapeutic options. These models administer a single cycle of PTX to induce a PIPN phenotype of mechanical and cold hypersensitivity that resolves within 28 days. However, these models do not mirror the clinical dosing regimen or generate a PIPN phenotype that reflects the patient experience. We developed a novel model of PIPN in rodents where repeated cycles of PTX are administered to mimic the clinical dosing regimen. Our aim in this study was to conduct a comprehensive and longitudinal behavioral profile of our novel model of PIPN in mice.</p><p><strong>Methods: </strong>We used our novel model in which three consecutive cycles of PTX (4 mg/kg, 4 doses per cycle) were administered to mimic the clinical dosing regimen in male and female C57Bl/6J mice. We assessed evoked responses, spontaneous behaviors, and normal rodent behaviors throughout PTX administration.</p><p><strong>Results: </strong>Repeated cycles of PTX caused long-lasting mechanical and cold hypersensitivity in male and female mice. PTX administration did not impact overall health, normal rodent behavior, proprioception, or motor function.</p><p><strong>Discussion: </strong>We show that administration of three consecutive PTX cycles generates a clinically relevant phenotype of PIPN, where repeated PTX cycles increase the duration of mechanical and cold hypersensitivity.</p><p><strong>Conclusion: </strong>Our findings support the use of this translational model to facilitate an improved understanding of PIPN and the development of effective treatment options. Improved pain management will enable the completion of cancer treatment, decrease health care expenditure, decrease mortality, and improve the quality of life for cancer patients and survivors.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intra-Arterial Transplantation of Human Glial Progenitor Cells Promotes Neurogenesis and Functional Recovery After Experimental Traumatic Brain Injury.","authors":"Anastasia K Sudina, Daria D Namestnikova, Elvira A Cherkashova, Mikhail E Ivanov, Ilya L Gubsky, Margarita O Shedenkova, Ekaterina V Belousova, Oleg V Makhnach, Timur H Fatkhudinov, Vladimir P Chekhonin, Dmitry V Goldshtein, Denis N Silachev, Diana I Salikhova","doi":"10.2174/011570159X427304251212103843","DOIUrl":"https://doi.org/10.2174/011570159X427304251212103843","url":null,"abstract":"<p><strong>Introduction: </strong>Traumatic brain injury presents a significant challenge, characterized by complex pathologies including neuroinflammation and axonal degeneration with limited treatment options. One of the promising areas of traumatic brain injury treatment is cell therapy. However, a critical aspect of this therapy is the method of stem/progenitor cell administration. This study aimed to evaluate the therapeutic potential of glial progenitor cells derived from induced pluripotent stem cells after intra-arterial administration in an experimental model of traumatic brain injury of male Wistar rats.</p><p><strong>Methods: </strong>Neurological status was assessed using the limb-placing, cylinder, and beam walking tests. Lesion volume was quantified by magnetic resonance imaging. Markers of inflammation and neurogenesis were analyzed using immunofluorescence staining and quantitative reverse transcription polymerase chain reaction. Cell migration was tracked via magnetic resonance imaging and histology.</p><p><strong>Results: </strong>Intra-arterial administration provided targeted delivery of cells into the cerebral vasculature. The cells successfully crossed the blood-brain barrier, migrated into the brain parenchyma, and were detectable for up to 48 hours. Transplantation led to significant improvement in sensorimotor function, reduced neuroinflammation in the injured area, and promoted neurogenesis.</p><p><strong>Discussion: </strong>The observed therapeutic effects are likely mediated by the factors secreted by glial progenitor cells, which possess anti-inflammatory and regenerative properties (paracrine signaling effect) and/or by their transient interactions with the target cells (juxtacrine signaling effect).</p><p><strong>Conclusion: </strong>Glial progenitor cells derived from induced pluripotent stem cells and delivered via the intra-arterial route show promise for the treatment of traumatic brain injury by reducing inflammation and enhancing neurogenesis.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization of Emerging Trends and Hotspots in Immunotherapy for Glioblastoma: A Bibliometric Analysis (2000-2024).","authors":"Linnan Duan, Hailiang Wang, Yuanhao Liu, Chuheng Wang, Yining Liu, Yubo Wang","doi":"10.2174/011570159X359974250730180425","DOIUrl":"https://doi.org/10.2174/011570159X359974250730180425","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma (GBM) is a highly aggressive and recurrent primary tumor of the central nervous system with a poor prognosis. This study conducts a comprehensive bibliometric analysis to map research trends and collaborations in GBM immunotherapy, aiming to construct a systematic knowledge framework to inform future research directions and strategic planning in the field.</p><p><strong>Methods: </strong>A comprehensive search was conducted in the Web of Science Core Collection (WoSCC) database for analyses focused on immunotherapy for GBM from 2000 to 2024. CiteSpace software was used to visualize and analyze the data, which includes countries/regions, institutions, and authors, and to identify the co-occurrences, clusters, and trends of references and keywords.</p><p><strong>Results: </strong>A total of 3363 publications concerning immunotherapy for GBM were included in our research. There was a yearly increase in the volume of publications. Most researchers who contribute to these publications are American, Chinese, and German. The University of California System was the leading institution in terms of publication output. Co-occurrence and clustering analyses of references and keywords highlighted the stimulatory effects of various therapies on the tumor microenvironment and their impact on patient survival. Keyword analysis identified 'tumor microenvironment', 'landscape', 'immune infiltration', and 'mechanisms' as emerging areas of interest.</p><p><strong>Discussion: </strong>This study presents a bibliometric analysis of immunotherapy for GBM based on publications from the WoSCC database (2000-2024). We mapped global collaboration networks and identified key research trends, emerging disciplines, and major hotspots in the field.</p><p><strong>Conclusion: </strong>Over the past two decades, immunotherapy has shifted toward precision and personalization, yielding encouraging progress. In numerous studies, neoadjuvant therapies targeting immune checkpoints have demonstrated partial survival benefits and therapeutic advantages. Future research may focus on exploring more rationally designed combination immunotherapy strategies to improve patient benefit.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subjects Affected by Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) Elevated Brain-Derived Neurotrophic Factor (BDNF) Serum Levels.","authors":"Francesco Angelucci, Zuzana Nedelska, Daniela Imal, Vanesa Jurášová, Jakub Hort","doi":"10.2174/011570159X448255260220084137","DOIUrl":"https://doi.org/10.2174/011570159X448255260220084137","url":null,"abstract":"<p><strong>Introduction: </strong>Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) are neurodegenerative disorders with marked neuronal dysfunction and damage, accompanied by the accumulation of abnormal alpha-synuclein. Identifying the proteins involved in their specific neurodegenerative processes is important to understand shared or disease-specific mechanisms of neurodegeneration. Recent investigations into these disorders have revealed intriguing alterations in the functionality of neurotrophic factors, including and predominantly the Brain-Derived Neurotrophic Factor (BDNF). Thus, the aim of this study was to investigate the BDNF serum levels in two cohorts of DLB and MSA patients and compare them to those of healthy individuals. Investigating serum BDNF concentrations in these conditions may provide insights into aspects of the underlying mechanisms of neurodegeneration.</p><p><strong>Methods: </strong>Serum BDNF concentrations were determined using commercial enzyme-linked immunosorbent assays. All serum samples were tested in duplicate, and the reported BDNF concentrations were ng/ml.</p><p><strong>Results: </strong>The findings demonstrated a significant increase in serum BDNF levels in both DLB and MSA patients versus healthy subjects.</p><p><strong>Discussion: </strong>This increase may represent a compensatory neuroprotective response to ongoing neuronal damage or a reflection of disease-related pathophysiological mechanisms involving altered BDNF regulation.</p><p><strong>Conclusion: </strong>These findings contribute to a growing body of evidence implicating neurotrophic fac-tor dysregulation in the pathogenesis of α-synucleinopathies. Moreover, the findings highlight BDNF as a potential therapeutic target and a candidate adjunct biomarker for diagnosis, monitoring disease activity, or treatment response. Additional experiments will clarify this causal relationship and the utility of BDNF-based interventions in modifying the disease trajectories in DLB and MSA.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Basis Underlying Changes of Brain Entropy and Couplings in Late-life Depression.","authors":"Meiling Chen, Hongjiang Zhang, Xiaohui Yu, Jie Zhang, Jingmei Zhong, Kexuan Chen, Rong Zi, Zhe Wu, Zhiyuan Wang, Kunhua Wu, Jiaojian Wang, Heng Shao, Ying Zhao, Baosheng Zhu","doi":"10.2174/011570159X385271251129225844","DOIUrl":"https://doi.org/10.2174/011570159X385271251129225844","url":null,"abstract":"<p><strong>Introduction: </strong>Late-life depression (LLD) with high prevalence accelerates cognitive impairment and becomes a risk factor for dementia, yet the pathogenesis of LLD is still largely unclear. Delineating the neuromolecular mechanism of LLD is of great significance to its etiology, early diagnosis, and precision treatment.</p><p><strong>Methods: </strong>This study included 35 patients with LLD and 41 age-matched healthy controls (HCs). Brain entropy (BEN) and functional connectivity (FC) were used to assess the abnormalities in brain functional system irregularity and couplings in LLD, using resting-state functional magnetic resonance imaging. Additionally, transcriptome and neurotransmitter data were employed to investigate the neuromolecular mechanisms underlying these changes.</p><p><strong>Results: </strong>Compared with HCs, patients with LLD exhibited significantly reduced BEN in the temporoparietal junction (TPJ) and decreased FC between TPJ and the middle frontal gyrus (MFG). Moreover, the changes of BEN were closely associated with the genes' expression profiles, which were involved in endocannabinoid, adrenergic, oxytocin, and cGMP-PKG signaling, glutamatergic, GABAergic, dopaminergic, cholinergic, serotonergic synapses, long-term potentiation, and long-term depression. We also found that the changes of BEN and FC were correlated with neurotransmitterreceptor distribution patterns of serotonin, histamine, acetylcholine, and dopamine.</p><p><strong>Discussion: </strong>Reduced BEN of TPJ in LLD indicates impaired regional information-processing complexity, potentially driving persistent cognitive deficits and abnormal negative-emotion handling, even in early LLD without overt clinical symptoms. Decreased TPJ-MFG FC disrupts brain network synchronization, weakening MFG-mediated emotion regulation and cognition, and possibly elevating the risk of suicidal ideation. Some genes, such as PRKACA/PRKACB, GNAI1, MAPK-ERK, PLA2G4A, and LXN, along with neurotransmitter receptors, contribute to a more comprehensive understanding of LLD. Altered brain entropy and connectivity in the TPJ-MFG circuit and related neurobiomolecules may underlie the pathogenesis of LLD and provide predictive value for its diagnosis and treatment.</p><p><strong>Conclusion: </strong>Our study highlights the important role of the TPJ-MFG circuit in the neuropathology of LLD and links the macroscopic functional abnormalities with transcriptome and neurotransmitter to establish the molecular basis. Our findings contribute to understanding the neurobiological basis of LLD and may facilitate future precision therapy.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}