BMC Neuroscience最新文献

{"title":"Investigating effects of day-to-day variations in environmental exposure on the human brain: study protocol for the Day2Day Environment project.","authors":"Kim Falkenstein, Claire Pauley, Simone Kühn","doi":"10.1186/s12868-026-01052-z","DOIUrl":"10.1186/s12868-026-01052-z","url":null,"abstract":"<p><strong>Background: </strong>Understanding how daily environmental exposures influence the human brain and mental health is increasingly important in the context of global urbanization and climate change. Previous studies have focused primarily on long-term environmental factors or isolated features like green space and air quality, neglecting the interaction between multiple exposures encountered in everyday life. This protocol paper describes the study design and dataset of the Day2Day Environment project, an ongoing study investigating how real-world, day-to-day environmental variability affects brain structure, function, and well-being.</p><p><strong>Methods: </strong>This dense longitudinal study collects multimodal data from 30 participants over 25 testing sessions, including neuroimaging and tracking of physiological, behavioral, and environmental variables. Using wearable devices, geographic ecological momentary assessments, and GPS-based geospatial tracking, we collect data on air quality, noise, light exposure, physical activity, stress, cognition, and affect. Neuroimaging measures include T1- and T2*-weighted images during rest and tasks, quantitative multi-parameter mapping, high-resolution proton density imaging of the hippocampus, and diffusion tensor imaging sequences.</p><p><strong>Conclusion: </strong>The Day2Day Environment dataset offers a unique opportunity to study short-term neuroplasticity in response to the dynamic interplay between multiple environmental exposures. Furthermore, the diversity of measurements in this dataset may be valuable for addressing research questions beyond environmental neuroscience.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029711","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":"Structural characteristics of local cortical networks wired by distance dependent connectivity rules.","authors":"Bernhard Hellwig","doi":"10.1186/s12868-026-01050-1","DOIUrl":"10.1186/s12868-026-01050-1","url":null,"abstract":"<p><strong>Background: </strong>The function of the cerebral cortex is shaped by its anatomical connectivity, yet experimental findings on connection probabilities in local cortical networks remain inconsistent. This study explores structural characteristics of local cortical networks based on distance dependent, Gaussian connectivity profiles. Monolayers of 101 × 101 pyramidal neurons were examined. Their connectivity was based on experimental anatomical or electrophysiological data. In the anatomical setting the connection probability between neighboring neurons was 0.8. In the electrophysiological scenario connection probabilities for adjacent neurons ranged between 0.08 and 0.23. All distance dependent networks were compared to the configuration model which generates degree-preserving but otherwise randomly rewired networks. The networks thus constructed were analyzed applying tools of network science, i.e. average degrees, degree distributions, local clustering coefficients and graph distances. Moreover, the numbers, sizes and spatial dimensions of cliques were investigated as well as the cost of connectivity.</p><p><strong>Results: </strong>Distance-dependent networks differed fundamentally from configuration-model networks across all structural measures. They showed substantially higher local clustering, formed more numerous and more spatially compact groups of strongly connected neurons, and required lower wiring cost. Importantly, the structure of distance-dependent networks was highly sensitive to near-neighbor connectivity: when neurons had a high probability of connecting locally, the network reliably developed tightly wired, spatially localized neuronal clusters.</p><p><strong>Conclusions: </strong>Distance-dependent connectivity gives rise to structural network features that may facilitate the emergence of functional neuronal assemblies. Based on the findings of this study, a general probabilistic rule for local cortical connectivity is proposed that can be used to design artificial neural networks with biologically inspired wiring principles.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007852","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":"Microglia-associated Galectin-3 expression in prenatal stress-induced cognitive dysfunction in adult offspring.","authors":"Qianqian Wang, Huanhuan Luo, Fangfei Fan, Zibin Zhao, Dandan Liu, Libin Liao, Shengbin Bai","doi":"10.1186/s12868-026-01048-9","DOIUrl":"10.1186/s12868-026-01048-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To characterize Galectin-3 expression and its cellular distribution in the hippocampus and prefrontal cortex of adult offspring exposed to prenatal stress, and to examine their associations with microglial activation, neuroinflammation, and cognitive dysfunction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Twelve pregnant Sprague-Dawley rats were randomly assigned to a stress group (n = 6) or a control group (n = 6). Rats in the stress group were subjected to restraint stress from gestational day 15 to day 21, whereas rats in the control group received no intervention. Cognitive function in adult offspring was assessed using the open-field test, elevated plus maze test, novel object recognition test, and Y-maze test. An enzyme-linked immunosorbent assay (ELISA) was used to measure peripheral blood levels of corticotropin-releasing hormone (CRH) and corticosterone (CORT) in dams and offspring. ELISA was used to measure the expression levels of inflammatory cytokines in the serum of offspring, while quantitative real-time PCR (qRT-PCR) was applied to detect the mRNA expression levels of inflammatory cytokines in the hippocampus, and prefrontal cortex of offspring. Immunofluorescence staining was used to evaluate microglial activation by assessing Iba1-positive microglial morphology and quantifying Iba1/CD68 double-positive cells, as well as to examine the colocalization of Iba1 with Galectin-3 in the hippocampus and prefrontal cortex of offspring. qRT-PCR was used to determine Galectin-3 mRNA expression levels in the hippocampus and prefrontal cortex of offspring. Western blotting was performed to assess the protein expression levels of Galectin-3, NF-κB p65, and the neuronal marker NeuN in the hippocampus and prefrontal cortex of offspring.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with the control group, offspring in the prenatal stress group exhibited significant behavioral impairments in the open-field test, elevated plus maze test, novel object recognition test, and Y-maze test. ELISA results showed that prenatal stress increased peripheral blood levels of CRH and CORT in both dams (P &lt; 0.05) and offspring (P &lt; 0.001). ELISA and qRT-PCR analyses further revealed significantly increased expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood, hippocampus and prefrontal cortex of offspring (P &lt; 0.05). Immunofluorescence staining demonstrated that prenatal stress induced activation-associated morphological changes in Iba1-positive microglia and significantly increased the numbers of Iba1/CD68 double-positive cells in the hippocampus and prefrontal cortex (all P &lt; 0.01). The numbers of Iba1/Galectin-3 double-positive cells were also significantly increased in the hippocampus (P &lt; 0.05) and prefrontal cortex (P &lt; 0.001). qRT-PCR and Western blot analyses showed that prenatal stress significantly upregulated Galectin-3 expression in the hippocampus and prefrontal corte","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073417","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":"Oral sodium butyrate alleviates motor deficits and dopaminergic neuronal loss in 6-hydroxydopamine-induced Parkinson's disease rat model.","authors":"Shun-Tai Yang, Yang-Ching Chen, Tzu-Jen Kao, Chi-Wei Kuo, Ching-Lu Chen, Shu-Wei Huang, Shu-Yu Chung, Hsien-Yu Fan, Wan-Ling Tsai","doi":"10.1186/s12868-026-01046-x","DOIUrl":"10.1186/s12868-026-01046-x","url":null,"abstract":"<p><strong>Background: </strong>Short-chain fatty acids regulate intestinal homeostasis and modulate the gut-brain axis, suggesting they may be applicable in adjunctive treatments for Parkinson's disease (PD). However, the therapeutic efficacy of sodium butyrate (NaB) in PD remains unclear. Using appropriate PD animal models may aid in clarifying the therapeutic effects of NaB and facilitate the development of NaB-based PD treatment strategies. We comprehensively evaluated the therapeutic effects of oral NaB in rats with 6-hydroxydopamine (6-OHDA)-induced PD.</p><p><strong>Methods: </strong>We induced hemiparkinsonism in rats by administering unilateral 6-OHDA in the medial forebrain bundle. At 24 h after confirming lesion development, some rats were randomized to receive oral NaB (administered daily) over 4 weeks. Behavioral assessments-comprising gait analysis, open-field activity, and apomorphine-induced rotations-were performed longitudinally in weeks 1 and 4. Finally, dopaminergic neuronal degeneration was evaluated to correlate functional recovery with structural neuroprotection.</p><p><strong>Results: </strong>The 4-week oral NaB intervention significantly alleviated 6-OHDA-induced motor deficits (i.e., locomotor activity, akinesia, and gait) and anxiety-like behavior; however, it did not alleviate apomorphine-induced rotations. Tyrosine hydroxylase immunohistochemical staining confirmed these findings, indicating that the dopaminergic neuron survival rate was significantly higher in the NaB-treated groups than in the sham control group.</p><p><strong>Conclusions: </strong>Early long-term oral NaB treatment afforded neuroprotection and alleviated motor and non-motor deficits (such as gait and central time in the open field) in rats with 6-OHDA-induced PD. Our model indicates the therapeutic potential of oral NaB and provides a translational framework for investigating the mechanisms of NaB therapy in PD and associated neurological disorders.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126737","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":"Correction: Effects of repetitive mechanical tactile stimulation interventions with stationary and moving patterns on paired-pulse depression.","authors":"Hiraku Watanabe, Sho Kojima, Naofumi Otsuru, Hideaki Onishi","doi":"10.1186/s12868-026-01040-3","DOIUrl":"10.1186/s12868-026-01040-3","url":null,"abstract":"","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905083","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":"A single-cell atlas of intracranial aneurysm progression identifies a dysfunctional VSMC subpopulation associated with rupture risk.","authors":"Xiangrong Chen, Bikun Liu, Xiaofeng Zhou, Zongtao Wu, Dongze Xu, Jingcheng Zhan, Jinliang Liu, Mao Ling, Fan Liu","doi":"10.1186/s12868-026-01029-y","DOIUrl":"https://doi.org/10.1186/s12868-026-01029-y","url":null,"abstract":"<p><strong>Background: </strong>Intracranial aneurysm (IA) rupture is a life-threatening event. While inflammation is implicated, the cellular mechanisms associated with progression from stable lesion to rupture remain poorly defined at single-cell resolution.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) on a mouse model spanning sham, formed, and ruptured IA stages. Computational analyses included trajectory inference, cell-cell communication analysis, and metabolic scoring. Key findings were validated using human IA bulk RNA-seq data and protein-level assays on matched clinical tissues.</p><p><strong>Results: </strong>Our single-cell atlas revealed a progressive \"inflammatory-lytic\" microenvironment marked by immune cell infiltration and vascular smooth muscle cell (VSMC) depletion. We identified a metabolically specialized VSMC subpopulation (VSMC_0) that was selectively lost in formed and ruptured aneurysms. Pseudotime analysis indicated VSMC differentiation blockade, associated with downregulation of the structural genes actin alpha2, smooth muscle (ACTA2) and prolyl 4-hydroxylase subunit alpha2 (P4HA2), which correlated with irregular aneurysm shape a strong clinical predictor of rupture risk. Cell communication analysis positioned VSMC_0 as a signaling hub to macrophages, suggesting a feed-forward inflammatory loop. These findings were validated in human IAs tissues.</p><p><strong>Conclusion: </strong>Our study identifies VSMC phenotypic dysregulation as a key correlate of IA instability, linking molecular deficits to clinical rupture predictors. This reframes IA as a disorder of vascular cellular identity and communication, revealing potential therapeutic targets for aneurysm stabilization.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β2 exerts neuroprotective effects via inhibition of astrocyte-mediated inflammatory responses.","authors":"Wen Li, Qiannan Zhang, Jiajia Shao, Qiao Jiang, Jiale Gu, Ruoxin Shi, Fangyixiao Xu, Youming Lu, Chuanyu Cang, Chen Liang, Xiao Han, Xinhua Zhang","doi":"10.1186/s12868-026-01025-2","DOIUrl":"10.1186/s12868-026-01025-2","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a severe neurological condition associated with complex pathological cascades. Transforming growth factor-β2 (TGF-β2) is a pleiotropic cytokine that participates in multiple cellular events in the central nervous system; however, its potential protective role and molecular mechanisms in the context of TBI-induced neuronal injury have not been fully elucidated. In this study, we observed that TGF-β2 expression was markedly increased following TBI, with peak expression at day 7 post-injury. Using an in vitro LPS-induced inflammatory model, we found that exogenous TGF-β2 treatment significantly reduced the expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6, as assessed by qRT-PCR, Western blot, and ELISA. Co-culture of neurons with conditioned medium from LPS-stimulated astrocytes revealed that TGF-β2 overexpression indirectly attenuated neuronal apoptosis and enhanced neuronal viability, as demonstrated by CCK-8, TUNEL staining, and molecular analyses. Mechanistic investigations suggested that the anti-inflammatory and anti-apoptotic effects of TGF-β2 may be mediated through activation of the Smad3 signaling pathway. Consistently, in vivo experiments indicated that TGF-β2 overexpression alleviated motor dysfunction and reduced neuronal apoptosis in a TBI mouse model. Collectively, these findings provide evidence for a protective role of TGF-β2 in inflammatory neuronal injury and offer insights into potential molecular targets for TBI therapeutic development.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"27 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191294","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":"Cholinergic inhibition disrupts retrieval-specific phosphorylation of CaMKII-α and CaMKII-β alongside ERK hyperactivation in the hippocampus during novel object recognition memory.","authors":"Majid Reza Farrokhi, Alireza Askari, Roksana SoukhakLari, Maryam Moosavi","doi":"10.1186/s12868-026-01027-0","DOIUrl":"10.1186/s12868-026-01027-0","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD), the most common form of dementia, is characterized by cholinergic dysfunction and early impairments in episodic and recognition memory. Although retrieval failure represents a hallmark of cognitive decline in AD, the task- and phase-specific molecular mechanisms underlying cholinergic-dependent memory retrieval remain poorly defined.</p><p><strong>Objective: </strong>This study investigated whether acute muscarinic cholinergic blockade disrupts the retrieval phase of recognition memory. We also examined the associated regulation of hippocampal calcium/calmodulin-dependent protein kinase II (CaMKII) isoforms α and β, together with extracellular signal-regulated kinase (ERK) signaling.</p><p><strong>Methods: </strong>Adult male SWR/J mice were trained in the NOR paradigm and administered scopolamine (1 mg/kg, i.p.) or saline 30 min prior to the retrieval phase. Recognition memory performance was assessed using the discrimination index and exploratory preference. Immediately following behavioral testing, hippocampal tissue was collected for Western blot analysis of phosphorylated and total CaMKII-α, CaMKII-β, and ERK.</p><p><strong>Results: </strong>Scopolamine significantly impaired recognition memory retrieval, as evidenced by a reduced discrimination index and decreased preference for the novel object, without diminishing overall exploratory activity. At the molecular level, scopolamine-induced cholinergic inhibition selectively decreased hippocampal phosphorylation of both CaMKII-α and CaMKII-β while increasing ERK phosphorylation, with no significant changes in total protein expression of any kinase.</p><p><strong>Conclusions: </strong>These findings identify a retrieval-specific, scopolamine-induced molecular signature of cholinergic inhibition in the hippocampus, characterized by concurrent suppression of both CaMKII isoform activities (α and β) alongside dissociable ERK hyperactivation. By extending prior molecular observations from aversively motivated paradigms to an ethologically relevant model of recognition memory, this study provides mechanistic insight into how cholinergic dysfunction contributes to memory retrieval deficits and suggests that cholinergic signaling maintains the functional (CaMKII-α) and structural (CaMKII-β) dimensions of hippocampal memory retrieval machinery through coordinated kinase activation.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535144","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":"Leucettine L41 Ameliorates Tau pathology and neuroinflammation in Parkinson's disease models.","authors":"Subin Hwang, Hyunha Choi, Hyeyeon Cho, Sunjoo Ahn, Hwi-Yeol Yun, Jin Sook Song","doi":"10.1186/s12868-026-01026-1","DOIUrl":"10.1186/s12868-026-01026-1","url":null,"abstract":"<p><strong>Background: </strong>Aberrant protein phosphorylation and sustained neuroinflammatory activation are key biochemical features of experimental parkinsonism. Dysregulated tau processing and excessive microglial reactivity have been implicated in motor dysfunction associated with dopaminergic injury. In the present study, we evaluated the biochemical and functional effects of Leucettine L41 using biochemical, cellular, and in vivo systems.</p><p><strong>Results: </strong>In an in vitro tau aggregation assay, L41 reduced the ThT fluorescence, indicating the suppression of fibril formation. In SH-SY5Y neuronal cells, L41 decreased tau phosphorylation at the Ser202/Thr205 site. In lipopolysaccharide-stimulated BV-2 microglial cells, L41 suppressed the production of nitric oxide, TNF-α, IL-1β, and IL-6, demonstrating its anti-inflammatory activity. Notably, L41 did not prevent toxin-induced neuronal cytotoxicity, suggesting that its primary action may not involve direct neuroprotection. In an MPTP-induced mouse model of Parkinson's disease, systemic L41 administration improved motor performance, accompanied by reduced tau phosphorylation and attenuated microglial activation in brain tissue.</p><p><strong>Conclusions: </strong>These findings indicate that L41 modulates tau aggregation, phosphorylation, and neuroinflammatory signaling in experimental parkinsonism, in association with functional motor improvement.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435041","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":"Plasma exosomal HERV-K transcripts are increased in amyotrophic lateral sclerosis.","authors":"Triparna Roy, Misha Ramesh, Nurul Aisha Ahmad Nizam, Steven Tandiono, Khuloud T Al-Jamal, Ammar Al-Chalabi, Alfredo Iacoangeli, Ahmad Al Khleifat","doi":"10.1186/s12868-026-01014-5","DOIUrl":"10.1186/s12868-026-01014-5","url":null,"abstract":"<p><p>Human endogenous retrovirus-K (HERV-K) reactivation is increasingly implicated in amyotrophic lateral sclerosis (ALS), with ongoing clinical trials investigating antiretroviral therapies. However, there is limited understanding of how HERV-K is trafficked in peripheral biofluids, and the role of exosomes, nano-sized extracellular vesicles, in this process remains largely unexplored. Exosomes offer a stable and cell-specific cargo reservoir that may reflect central pathogenic processes and serve as a minimally invasive biomarker source. In this study, we isolated plasma-derived exosomes from ALS patients (n = 21) and healthy controls (n = 16), and quantified exosomal HERV-K gag, env, and pol transcript levels using SYBR Green qPCR with RNase treatment and normalization to both traditional and exosome-enriched reference genes. HERV-K pol expression was significantly elevated in ALS, with fold-changes ranging from 1.59 to 1.85 (P = 0.037-0.051). env and gag also showed increased expression, though with greater variability. Normalization to the exosome-specific gene SOD2 provided the most consistent signal. These findings suggest that exosomal HERV-K transcripts, particularly pol, could serve as accessible biomarkers for patient stratification and treatment monitoring in HERV-K-targeted ALS trials. This work establishes proof-of-concept for using exosomal cargo to track endogenous retroviral activity in neurodegeneration and supports further investigation of liquid biopsy approaches in ALS precision medicine.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13359462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418428","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}