IBRO Neuroscience Reports最新文献

{"title":"The miR-133b and miR-206 serum levels as a candidate biomarker in Alzheimer's patients with dyslipidemia","authors":"Shahram Darabi ,&nbsp;Enam Alhagh Gorgich ,&nbsp;Auob Rustamzadeh ,&nbsp;Nafiseh Mohebi ,&nbsp;Hossein Mozhdehipanah","doi":"10.1016/j.ibneur.2025.04.014","DOIUrl":"10.1016/j.ibneur.2025.04.014","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by cognitive decline. Dyslipidemia, a risk factor for AD, may influence the expression of microRNAs (miRs) involved in AD pathogenesis. Thus, the aim of this study was to investigate the effect of dyslipidemia on the expression levels of miR-133b and miR-206 in AD patients with mild cognitive impairment. This study recruited a total of 45 subjects, who were subsequently divided into three distinct groups: the AD group (n = 15), the AD dyslipidemia group (n = 15), and the dyslipidemia group with normal cognitive status (n = 15). The Aβ_42/40 serum ratio was measured using an enzyme-linked immunosorbent assay. miR expression levels were determined by RT-qPCR. Clinicopathological characteristics, including Mini-Mental State Examination (MMSE) scores, Clinical Dementia Rating (CDR), and HDL levels, were also assessed. miR-133b levels were significantly reduced in the AD dyslipidemia group compared to the other two groups (p &lt; 0.001), while miR-206 levels were markedly elevated (p &lt; 0.001). Spearman correlation analysis revealed that miR-133b expression levels were positively associated with the Aβ_42/40 ratio (r = 0.799), MMSE scores (r = 0.578), and HDL levels (r = 0.768), while negatively associated with miR-206 levels (r = -0.461), CDR score (r = -0.539), and AD duration (r = -0.569). Conversely, miR-206 levels positively correlated with CDR and disease duration, but were inversely associated with miR-133b, MMSE, Aβ_42/40, and HDL. Serum miR-133b and miR-206 levels appear to be associated with AD pathology and clinical parameters in the early stages of the disease. The studied miR expression levels could serve as reliable biomarkers in AD patients with dyslipidemia.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 672-678"},"PeriodicalIF":2.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of modified scooter board therapy on trunk control and hip muscle activation in children with cerebral palsy – A pilot randomised control study","authors":"Shreekanth D. Karnad ,&nbsp;Amitesh Narayan ,&nbsp;Nutan Kamath ,&nbsp;Bhamini Krishna Rao ,&nbsp;Monika Sharma ,&nbsp;Vijaya Kumar K","doi":"10.1016/j.ibneur.2025.04.009","DOIUrl":"10.1016/j.ibneur.2025.04.009","url":null,"abstract":"<div><div>Cerebral palsy (CP), with an incidence rate of 2.95, is one of the leading causes of disability in children. The excessive tone in several muscle groups causes significant movement deficits and secondary impairments, such as hip displacement, affecting quality of life. Although age-related functional positioning treatment is effective, it does not prevent secondary deficits. Literature recommends the use of task-based training with an emphasis on the functional elongation of these spastic muscle groups. Thus, a therapy that is engaging, parent-inclusive, and addresses hip-related deficits is needed. Hence, this study aimed to develop and evaluate a therapy targeting adductor overactivity and trunk control. Modified Scooter Board Therapy (MSBT) is an intervention that uses a specially designed scooter board device, allowing children to propel themselves forward while positioned prone with hip abduction and neutral hip rotation. A convenient sample of eight children with CP were assigned to either the MSBT or conventional exercise group. The intervention lasted eight weeks, and electromyographic (EMG) recordings at rest and during volitional activity were obtained at baseline and after eight weeks. Non-parametric statistical analysis, with a significance level of p &lt; 0.05, showed no statistically significant differences between the groups at the end of the eight weeks. However, volitional hip adductor activity significantly changed in the MSBT group, indicated by a reduction in mean motor unit potential at rest. Additionally, parents preferred MSBT for its ease of use. Thus, MSBT appears to be a clinically promising intervention to reduce adductor hypertonicity and improve active control, highlighting the importance of prone positioning with active elongation for better motor function.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 705-713"},"PeriodicalIF":2.0,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Mapping of Brain COX-1 with [11C]PS13: Pharmacokinetic Evidence from human PET Imaging","authors":"Kiana Orangi ,&nbsp;Kimiya Batebi ,&nbsp;Farnoosh Vosough ,&nbsp;Mahdiyeh Nozad Varjovi ,&nbsp;Fatemeh Salehian ,&nbsp;Sahar Mesbah ,&nbsp;Mehrnaz Salahi ,&nbsp;Sajjad Hajihosseini ,&nbsp;Mohammad Yousef Fazel ,&nbsp;Saman Zaman ,&nbsp;Reza Hossein Zadeh ,&nbsp;Alaleh Alizadeh ,&nbsp;Mahsa Asadi Anar ,&nbsp;Niloofar Deravi","doi":"10.1016/j.ibneur.2025.04.012","DOIUrl":"10.1016/j.ibneur.2025.04.012","url":null,"abstract":"<div><h3>Background and aim</h3><div>Arachidonic acid is converted by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) to prostaglandin H2, which has proinflammatory properties. The new PET radioligand [11 C]PS13 exhibits superior in vivo selectivity for COX-1 in nonhuman primates compared to COX-2. This study aimed to investigate [11 C]PS13 pharmacologically selectivity and substantial binding to COX-1 in the human brain.</div></div><div><h3>Material and methods</h3><div>Eight healthy volunteers had baseline [11 C]PS13 brain PET scans, and then images were blocked with either aspirin, celecoxib, or ketoprofen. The participants underwent two 90-minute [11 C]PS13 PET scans with radio metabolite-corrected arterial input function at baseline and approximately two hours after they received 75 mg of ketoprofen orally</div></div><div><h3>Result</h3><div>This study on [11 C]PS13 brain PET scans showed that ketoprofen and celecoxib selectively bind to COX-1 in the human brain. The occupancy plot showed a positive correlation with plasma ketoprofen concentration, with the highest binding potentials in the calcarine and lingual gyrus of the occipital region. The occupancy for COX-1 was about 49 % and 27 % for ketoprofen and celecoxib, respectively.</div></div><div><h3>Conclusion</h3><div>Ketoprofen demonstrated the highest selectivity for COX-1, while celecoxib exhibited partial occupancy likely due to dose- or time-dependent COX-1 inhibition. Aspirin showed minimal effect. Given the small sample size (n = 8), further studies with larger cohorts are warranted to confirm these findings and assess pharmacokinetic influences more thoroughly.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 657-662"},"PeriodicalIF":2.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic characterization of maturing neurons from human neural stem cells across developmental time points","authors":"Kimia Hosseini ,&nbsp;Gaëtan Philippot ,&nbsp;Sara B. Salomonsson ,&nbsp;Andrea Cediel-Ulloa ,&nbsp;Elnaz Gholizadeh ,&nbsp;Robert Fredriksson","doi":"10.1016/j.ibneur.2025.04.013","DOIUrl":"10.1016/j.ibneur.2025.04.013","url":null,"abstract":"<div><div>Neurodevelopmental studies employing animal models encounter challenges due to interspecies differences and ethical concerns. Maturing neurons of human origin, undergoing several developmental stages, present a powerful alternative. In this study, human embryonic stem cell (H9 cell line) was differentiated into neural stem cells and subsequently matured into neurons over 30 days. Ion AmpliSeq™ was used for transcriptomic characterization of human stem cell-derived neurons at multiple time points. Data analysis revealed a progressive increase of markers associated with neuronal development and astrocyte markers, indicating the establishment of a co-culture accommodating both glial and neurons. Transcriptomic and pathway enrichment analysis also revealed a more pronounced GABAergic phenotype in the neurons, signifying their specialization toward this cell type. The findings confirm the robustness of these cells across different passages and demonstrate detailed progression through stages of development. The model is intended for neurodevelopmental applications and can be adapted to investigate how genetic modifications or exposure to chemicals, pharmaceuticals, and other environmental factors influence neurons and glial maturation.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 679-689"},"PeriodicalIF":2.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gliogenesis but not neurogenesis occurs during the acute phase of vestibular compensation after unilateral vestibular neurectomy","authors":"Liang-Wei Chen ,&nbsp;Kenneth Lap-Kei Wu ,&nbsp;Kin-Wai Tam ,&nbsp;Chun-Wai Ma ,&nbsp;Yat-Ping Tsui ,&nbsp;Chun-Hong Lai ,&nbsp;Ying-Shing Chan ,&nbsp;Daisy Kwok-Yan Shum","doi":"10.1016/j.ibneur.2025.04.008","DOIUrl":"10.1016/j.ibneur.2025.04.008","url":null,"abstract":"<div><div>Following unilateral loss of vestibular input, recovery of motor symptoms is achieved within 2 weeks in rodents. Given that neurogenesis was only reported at 1 month post-lesion, whether there is neurogenesis in this early phase of vestibular compensation remains to be investigated. If not, what then is the major cell type that participates in this timeframe? We show abundant nestin-positive cells in the ipsilesional but not contralesional vestibular nucleus (VN) of rats after ablating cell bodies of vestibular nerve at the Scarpa’s ganglion, as confirmed by both magnetic resonance imaging after surgery and histology. Bromodeoxyuridine (BrdU) uptake indicated that these cells actively proliferated. A high proportion of the cells were double-positive for nestin and GFAP as early as 4 days, and up to 2 weeks post-lesion, in contrast to none in control preparations. In contrast, the number of NeuN-positive neural lineage cells in the VN remained constant in both the control and lesioned rats. Furthermore, NeuN-positive cells were not positive for BrdU. However, a small number of proliferating cells stained positive for the immature neuron progenitor marker doublecortin. Taken together, we show that unilateral loss of vestibular input stimulates proliferation of neuroglial progenitors, and provide evidence that argues against occurrence of neurogenesis within the 2 week period in which recovery of postural and motor symptoms occurs.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 690-697"},"PeriodicalIF":2.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative emotion modulates postural tremor variability in Parkinson’s disease: A multimodal EEG and motion sensor study toward behavioral interventions","authors":"Kang Lin ,&nbsp;Pei Li ,&nbsp;Pei-zhu Zhang ,&nbsp;Ping Jin ,&nbsp;Xin-feng Ma ,&nbsp;Guang-an Tong ,&nbsp;Xiao Wen ,&nbsp;Xue Bai ,&nbsp;Gong-qiang Wang ,&nbsp;Yong-zhu Han","doi":"10.1016/j.ibneur.2025.04.003","DOIUrl":"10.1016/j.ibneur.2025.04.003","url":null,"abstract":"<div><h3>Background</h3><div>Despite clinical observations of emotion-tremor interactions in Parkinson’s disease (PD), the neurophysiological mechanisms mediating this relationship remain poorly characterized.</div></div><div><h3>Methods</h3><div>This study employs a multimodal approach integrating 16-channel electroencephalography (EEG) and inertial motion sensors to investigate emotion-modulated postural tremor dynamics in 20 PD patients and 20 healthy controls (HCs) during standardized video-induced emotional states (positive/neutral/negative).</div></div><div><h3>Results</h3><div>Key findings demonstrate impaired negative emotional processing in PD, manifested as paradoxical increases in subjective valence (pleasure-displeasure ratings) coupled with reduced physiological arousal. Tremor variability predominantly correlated with negative emotional states, showing a negative association with valence scores and positive correlation with arousal levels. EEG analysis identified differential beta-band power modulation in prefrontal (Fp1/Fp2) and temporal (T3/T4) regions during negative emotion processing. These results suggest that emotion-driven tremor fluctuations in PD originate from dysfunctional integration of limbic and motor networks.</div></div><div><h3>Conclusion</h3><div>These findings establish emotion-modulated tremor as a distinct PD phenotype, informing the development of closed-loop biofeedback systems for personalized neuromodulation.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 663-671"},"PeriodicalIF":2.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acupuncture regulates astrocyte neurotoxic polarization to protect blood–brain barrier integrity in delayed thrombolysis through mediating ERK1/2/Cx43 axis","authors":"Zhi-Hui Zhang ,&nbsp;Yu Gu ,&nbsp;Zheng Huang ,&nbsp;Xin-Yu Liu ,&nbsp;Wen-Tao Xu ,&nbsp;Xin-Chang Zhang ,&nbsp;Guang-Xia Ni","doi":"10.1016/j.ibneur.2025.04.005","DOIUrl":"10.1016/j.ibneur.2025.04.005","url":null,"abstract":"<div><h3>Background</h3><div>Thrombolytic therapy remains the standard treatment for acute ischemic stroke. The narrow window for thrombolysis means that delay in treatment worsens brain injury. Astrocytes regulate blood-brain barrier (BBB) integrity and neuroinflammation, yet their neurotoxic polarization exacerbates injury in neuropathological conditions, including ischemic stroke. Delayed recombinant tissue plasminogen activator (rt-PA) thrombolysis disrupts astrocyte homeostasis, further aggravating brain injury. This study investigates whether acupuncture, a key therapy in traditional Chinese medicine, alleviates delayed thrombolysis-induced injury by modulating astrocyte neurotoxic polarization and elucidates the underlying signaling pathway.</div></div><div><h3>Methods</h3><div>A rat model of embolic stroke with delayed rt-PA thrombolysis was established. The effects of infarct volume, BBB integrity, and neuroinflammation of acupuncture were evaluated. Bulk and single-cell transcriptomic analyses were performed to assess astrocyte-specific transcriptional changes. Western blotting, immunofluorescence, and pharmacological inhibition experiments validated molecular mechanisms.</div></div><div><h3>Results</h3><div>Acupuncture reduced infarct volume, improved neurological function, and restored BBB integrity. Transcriptomic analysis revealed dynamic regulation of astrocyte neurotoxic polarization following acupuncture intervention. Further validation experiments demonstrated that acupuncture suppressed the ERK1/2-Cx43 cascade, thereby attenuating astrocyte-mediated neurotoxicity. Pharmacological modulation of this pathway replicated the protective effects of acupuncture, highlighting the role in mitigating astrocyte dysfunction and promoting BBB recovery.</div></div><div><h3>Conclusion</h3><div>Acupuncture mitigates delayed thrombolysis-induced brain injury by modulating astrocyte polarization via the ERK1/2-Cx43 pathway. These findings highlight acupuncture as a potential strategy to enhance thrombolytic therapy safety in ischemic stroke.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 604-618"},"PeriodicalIF":2.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of circulating tumor DNA in brain tumor research","authors":"Amir Modarresi Chahardehi ,&nbsp;Niki Faraji ,&nbsp;Nikoo Emtiazi ,&nbsp;Reza Nasiri ,&nbsp;Maryam Daghagheleh ,&nbsp;Helia Mohammadaein ,&nbsp;Fatemeh Masoudi ,&nbsp;Kimia Ghazi Vakili ,&nbsp;Aylin Sefidmouy Azar ,&nbsp;Hossein Fatemian ,&nbsp;Hossein Motedayyen ,&nbsp;Reza Arefnezhad ,&nbsp;Fatemeh Rezaei-Tazangi ,&nbsp;Zahra Niknam ,&nbsp;Marziye Ranjbar Tavakoli","doi":"10.1016/j.ibneur.2025.04.007","DOIUrl":"10.1016/j.ibneur.2025.04.007","url":null,"abstract":"<div><div>Brain tumors provide considerable diagnostic and treatment challenges due to their intricate nature and the hazards linked to direct tissue biopsies. Owing to the restricted sensitivity and specificity of conventional procedures, new techniques like liquid biopsy have garnered attention. Circulating tumor DNA (ctDNA), present in physiological fluids such as cerebrospinal fluid (CSF) and plasma, has emerged as a viable instrument for non-invasive tumor characterization. Hence, advancements in next-generation sequencing (NGS) and digital PCR have enhanced the sensitivity of ctDNA detection, rendering it a feasible method for monitoring tumor dynamics and evaluating therapy responses. Research indicates that ctDNA strongly correlates with tumor heterogeneity, providing a superior alternative to single-site tissue biopsies. CSF, due to its proximity to the brain, offers elevated amounts of ctDNA for examination relative to plasma, particularly in central nervous system (CNS) cancers. Research indicates that ctDNA can detect actionable mutations, forecast little residual illness, and enable real-time monitoring of disease development and resistance. Notwithstanding these advantages, difficulties, including poor ctDNA yield and heterogeneity in detection methodologies persist. This review examines the clinical efficacy of ctDNA in brain tumor diagnosis, emphasizes technical developments in ctDNA analysis, and stresses the necessity for standardized methods. Comprehending the capabilities and constraints of ctDNA can facilitate the development of more accurate, individualized therapy approaches in neuro-oncology.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 714-725"},"PeriodicalIF":2.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of BMSCs overexpressing intelectin-1 on angiogenesis in rats with cerebral infarction","authors":"Bo Zhu,&nbsp;Kun Guo,&nbsp;Lei Zha,&nbsp;Zhengli Di,&nbsp;Hongwei Zhao,&nbsp;Le Chang,&nbsp;Naibing Gu","doi":"10.1016/j.ibneur.2025.03.012","DOIUrl":"10.1016/j.ibneur.2025.03.012","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral infarction (CI) is a common and frequently occurring acute neurological disease in clinical practice, posing a severe threat to human health. CI results from various causes leading to local cerebral tissue ischemia and hypoxia due to vascular occlusion and impaired blood supply, which in turn leads to tissue necrosis and corresponding clinical manifestations of neurological deficits. However, to date, treatment options for cerebral infarction remain limited. Therefore, it is crucial to rapidly establish collateral circulation to compensate for the occluded vessels and restore blood flow perfusion.</div></div><div><h3>Objective</h3><div>To assess the effect of bone marrow mesenchymal cells transfected with intelectin-1 (Itln-1) gene on the angiogenesis and apoptosis of CI.</div></div><div><h3>Method</h3><div>Lentiviral-mediated transfection of the Itln-1 gene into bone marrow mesenchymal stem cells (BMSCs) was performed, followed by intravenous injection into rats with CI through the tail vein. The volume of the CI, capillary density, and apoptotic cells were detected.</div></div><div><h3>Results</h3><div>With the increase of AKT and eNOS phosphorylation levels, BMSCs with overexpression Itln-1 gene could significantly promote angiogenesis and reduce the infarct volume in the ischemic penumbra. Meanwhile, the ratio of Bcl-2/Bax increased, and apoptotic cells decreased.</div></div><div><h3>Conclusion</h3><div>The overexpression of Itln-1 can effectively promote CI angiogenesis and inhibit cell apoptosis than transplantation of Itln-1 gene or MSCS alone</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 619-626"},"PeriodicalIF":2.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNF13 variants L311S and L312P associated with developmental epileptic encephalopathy alter dendritic organization in hippocampal neurons","authors":"Valérie C. Cabana ,&nbsp;Marc P. Lussier","doi":"10.1016/j.ibneur.2025.04.004","DOIUrl":"10.1016/j.ibneur.2025.04.004","url":null,"abstract":"<div><div>Developmental and epileptic encephalopathy (DEE) is a group of rare and serious neurological disorders where seizures exacerbate developmental impairment. Recently, genetic mutations in the <em>RNF13</em> gene were reported to cause DEE73. Specifically, two leucines from the ubiquitin E3 ligase RNF13 are converted to serine or proline (L311S and L312P). These mutations are located within a dileucine motif, which impairs RNF13's capacity to interact with AP-3. A second motif allows RNF13 to interact with AP-1 when the dileucine sorting motif is altered. The present study demonstrates that RNF13 variants L311S and L312P are trafficked through an AP-1-dependent pathway in HeLa cells. In cultures of primary rat hippocampal neurons, the protein level of the variants is significantly higher in dendrites than for wild-type protein. L311S and L312P variants alter dendritic components similarly to an RNF13 AP-3-defective binding variant or a dominant negative for RNF13’s ubiquitin ligase activity. Compared to non-transfected neurons, the variants change the distribution of EEA1-positive early endosomes throughout the dendrites. While the WT alters the distribution of lysosomes (Lamp1-positive) in dendrites, the variants only decrease their presence in proximal dendrites. Unlike the variants, RNF13 WT increases the abundance of PSD-95 in distal dendrites. Interestingly, only the variants with altered dileucine motifs decrease the total number of postsynaptic inhibitory protein Gephyrin puncta. This study reports that genetic variants L311S and L312P mainly act as a dominant negative protein. This research provides valuable insights into the dendritic defects that occur when DEE73-associated genetic variants of RNF13 are present.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 559-573"},"PeriodicalIF":2.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}