Neuroscience Letters最新文献

{"title":"Changes in adropin levels in brain and peripheral tissues with aging","authors":"Changjun Yang,&nbsp;John Aaron Howell,&nbsp;Lei Liu,&nbsp;Rachel E. Gunraj,&nbsp;Eduardo Candelario-Jalil","doi":"10.1016/j.neulet.2025.138150","DOIUrl":"10.1016/j.neulet.2025.138150","url":null,"abstract":"<div><div>Adropin is a bioactive peptide found in the brain and various peripheral tissues. Evidence suggests that aging significantly decreases brain adropin levels, and interventions that elevate adropin may help alleviate age-related neurological disorders such as ischemic stroke and cognitive decline. However, the impact of aging on peripheral tissue adropin levels and its relationship with the neural recognition molecule NB-3/contactin-6 in the brain remains unclear. In this study, we quantified adropin using immunoblotting in brain and peripheral tissues (liver, lung, kidney, spleen, ileum, colon) from young (8–10 weeks) and aged (18–20 months) male mice. Results indicated a significant decrease in brain adropin levels in aged mice, while peripheral tissues showed no significant changes compared to young controls. Additionally, levels of NB-3/contactin-6, a potential adropin receptor and Notch1 ligand, were lower in aged brains. Co-immunoprecipitation demonstrated that adropin physically associates with brain NB-3. Notably, the age-related reduction in brain adropin correlates with increased oxidative stress markers (gp91^phox and 4-hydroxynonenal). We provide the first evidence that aging is linked to a concurrent loss of adropin and NB-3 in the brain but not in peripheral tissues. Interventions to maintain brain adropin levels could help mitigate the brain’s aging process and alleviate age-related neurological dysfunction.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138150"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374330","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":"Synergistic effects of neural stem cells and ibrutinib on neural tissue repair and functional recovery in a contusion mouse model of spinal cord injury","authors":"Somayyeh Torabi ,&nbsp;Zahra Zeraatpisheh ,&nbsp;Seyed Hadi Anjamrooz ,&nbsp;Amir Ghanbari ,&nbsp;Syed Shadab Raza ,&nbsp;Hadi Aligholi ,&nbsp;Hassan Azari","doi":"10.1016/j.neulet.2025.138149","DOIUrl":"10.1016/j.neulet.2025.138149","url":null,"abstract":"<div><div>Modulating the immune response following spinal cord injury (SCI) is vital for establishing a conducive microenvironment that supports the survival and engraftment of transplanted neural stem/progenitor cells (NSPCs). Building on our prior findings of ibrutinib’s immunotherapeutic potential in acute SCI, this study investigates the impact of ibrutinib administration on NSPC survival, fate and their potential synergistic effects on tissue repair and motor function in a contusive mouse model of SCI.</div><div>Green fluorescence expressing NSPCs were transplanted into the lesion site with or without concurrent ibrutinib administration. Over four weeks, comprehensive assessments included behavioral evaluations, lesion volume measurements, and analyses of the survival, fate, and migration patterns of the transplanted cells. The results revealed that ibrutinib and NSPCs individually reduced lesion volume and improved motor functions. However, their combination significantly accelerated and enhanced motor recovery. Furthermore, ibrutinib improved cell viability, increasing markers for oligodendrocyte and neuroblast while concurrently diminishing the expression of astrocyte marker glial fibrillary acidic protein (GFAP).</div><div>In conclusion, the combined utilization of ibrutinib and NSPC transplantation presents a promising strategy for enhancing tissue repair, promoting functional recovery, and positively modulating cell behaviors in the context of SCI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138149"},"PeriodicalIF":2.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372658","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":"Pupillary unrest is attenuated in attention deficit hyperactivity disorder (ADHD)","authors":"Claudio M. Privitera ,&nbsp;Sean Noah ,&nbsp;Thom Carney ,&nbsp;Stanley A. Klein ,&nbsp;Agatha Lenartowicz ,&nbsp;Stephen P. Hinshaw ,&nbsp;James T. McCracken ,&nbsp;Joel T. Nigg ,&nbsp;Sarah L. Karalunas ,&nbsp;Rory C. Reid ,&nbsp;Mercedes Oliva ,&nbsp;Samantha S. Betts ,&nbsp;Gregory V. Simpson","doi":"10.1016/j.neulet.2025.138148","DOIUrl":"10.1016/j.neulet.2025.138148","url":null,"abstract":"<div><div>We investigated the phenomenon of pupillary unrest in individuals with Attention Deficit Hyperactivity Disorder (ADHD) compared to neurotypical controls. We measured the power of low-frequency pupil oscillations under two experimental conditions: a passive condition with minimal distraction and a resting condition with no distraction. The study included 76 adult participants (42 controls and 34 with ADHD) aged 18–40. The results show that individuals with ADHD exhibit reduced power in pupillary oscillations, suggesting a suppression of general catecholaminergic activity. The nature of the experiment indicates that this suppression is endemic in the background and independent of the visual task or the ongoing cognitive effort. This finding is consistent with our previous observations of reduced pupil dilations in ADHD during active tasks <span><span>[1]</span></span> and provide basic insights for future research aimed at developing and refining a psychophysical paradigm that could serve as a biomarker to enhance ADHD evaluation and classification.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138148"},"PeriodicalIF":2.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364543","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":"Higher level of [3H]UCB-J binding in ApoE Ɛ4 allele carriers with Alzheimer disease","authors":"Jens D. Mikkelsen ,&nbsp;Phoebe Linde-Atkins ,&nbsp;Burcu A. Pazarlar","doi":"10.1016/j.neulet.2025.138135","DOIUrl":"10.1016/j.neulet.2025.138135","url":null,"abstract":"<div><div>Neuronal and synapse losses are seen under the progression of Alzheimer’s disease (AD). Accordingly, the binding to the synaptic vesicle glycoprotein 2A (SV2A) using the selective radioligand [³H]UCB-J was found to be reduced in frontal cortex from patients with AD. We report here that the reduction in SV2A binding is highly significant only in patients not carrying the ApoE ɛ4 allele. By contrast, those individuals with one or two ApoE ɛ4 alleles had SV2A binding levels not different from controls. Because ApoE4 is an important genetic risk and strongly linked to late-onset AD, this study raises an interesting new and unexpected association to SV2A, synapse loss, and function.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138135"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122745","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":"Differential cortical aspartate uptake across the oestrous cycle is associated with changes in gut microbiota in Wistar-Kyoto rats","authors":"Jahangir Sajjad ,&nbsp;Jennifer Morael ,&nbsp;Thieza G. Melo ,&nbsp;Tara Foley ,&nbsp;Amy Murphy ,&nbsp;James Keane ,&nbsp;Jelena Popov ,&nbsp;Catherine Stanton ,&nbsp;Timothy G. Dinan ,&nbsp;Gerard Clarke ,&nbsp;John F. Cryan ,&nbsp;James M. Collins ,&nbsp;Siobhain M. O’Mahony","doi":"10.1016/j.neulet.2024.138096","DOIUrl":"10.1016/j.neulet.2024.138096","url":null,"abstract":"<div><div>Pain and psychological stress are intricately linked, with sex differences evident in disorders associated with both systems. Glutamatergic signalling in the central nervous system is influenced by gonadal hormones via the hypothalamic–pituitary–adrenal axis and is central in pain research. Emerging evidence supports an important role for the gut microbiota in influencing pain signalling. Here, the functional activity of excitatory amino acid transporters (EAATs) in the anterior cingulate cortex (ACC) and lumbosacral spinal cord of male and female Wistar-Kyoto rats, an animal model of comorbid visceral hypersensitivity and enhanced stress responsivity, was investigated across the oestrous cycle. Correlations between the gut microbiota and changes in the functional activity of the central glutamatergic system were also investigated.</div><div>EAAT function in the lumbosacral spinal cord was similar between males and females across the oestrous cycle. EAAT function was higher in the ACC of dioestrus females compared to proestrus and oestrus females. In males, aspartate uptake in the ACC positively correlated with <em>Bacteroides</em>, while aspartate uptake in the spinal cord positively correlated with the relative abundance of <em>Lachnospiraceae NK4A136</em>. Positive associations with aspartate uptake in the spinal cord were also observed for <em>Alistipes</em> and <em>Bifidobacterium</em> during oestrus, and <em>Eubacterium coprostanoligenes</em> during proestrus. <em>Clostridium sensu stricto1</em> was negatively associated with aspartate uptake in the ACC in males and dioestrus females.</div><div>These data indicate that glutamate metabolism in the ACC is oestrous stage-dependent and that short-chain fatty acid-producing bacteria are positively correlated with aspartate uptake in males and during specific oestrous stages in females.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138096"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882551","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":"Exposure to an enriched environment and fucoidan supplementation ameliorate learning and memory function in rats subjected to global cerebral ischemia","authors":"Ronyson Kharkongor,&nbsp;JenishaChris Stephen,&nbsp;UlfathTasneem Khan,&nbsp;Rameshkumar Radhakrishnan","doi":"10.1016/j.neulet.2024.138094","DOIUrl":"10.1016/j.neulet.2024.138094","url":null,"abstract":"<div><div>An enriched environment (EE) constitutes a proficient strategy that instigates social, cognitive, and motor faculties, fostering healing and heightening learning and memory function after ischemia, while fucoidan derived from brown seaweed encompasses a diverse array of bioactivities and is known to possess neuroprotective properties. This study aims to investigate the effectiveness of combining fucoidan and EE in a rat model of vascular dementia to overcome cognitive challenges. The rats were randomly assigned as Sham, Lesion − 4-vessel occlusion (4VO) i.e., transient global cerebral ischemia (tGCI), 4VO + F50mg/kg, 4VO + EE, and 4VO + F50mg/kg + EE. At the end of the study periods, the rats were exposed to the Novel object task, T-maze, and the Morris water maze. The profile of hippocampal pyramidal neurons and their dendrites was assessed through the CFV, and Golgi cox stained brain sections. Neuroinflammatory markers (IL-1β, IL-6, NF-κB, TNF-α) and synaptogenic markers (BDNF, SYP, PSD-95) were evaluated through western blot analysis. The levels of oxidative stress marker (LPO) and antioxidants (SOD, CAT, GSH, GST, GPX) in the hippocampus were quantified through biochemical assay. The findings revealed that the cognitive deficits were significantly reduced in both the 4VO + F50mg/kg and 4VO + F50mg/kg + EE treatment groups and inflammatory markers were reduced with increased antioxidant levels and synaptogenic markers when compared with the lesion group. However, through this study, the combination therapy involving fucoidan and exposure to an EE was proven effective in preserving neural integrity and restoring cognitive function against the damage caused by oxidative stress and inflammation following tGCI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138094"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907345","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":"Resveratrol ameliorates postoperative cognitive dysfunction in aged mice by regulating microglial polarization through CX3CL1/CX3CR1 signaling axis","authors":"Jinming Liu ,&nbsp;Yong Wang ,&nbsp;Hong Sun ,&nbsp;Daoyun Lei ,&nbsp;Jufeng Liu ,&nbsp;Yuanhui Fei ,&nbsp;Chunhui Wang ,&nbsp;Chao Han","doi":"10.1016/j.neulet.2024.138089","DOIUrl":"10.1016/j.neulet.2024.138089","url":null,"abstract":"<div><div>Postoperative cognitive dysfunction (POCD) is a common cognitive challenge faced by older adults. One of the key contributors to the development of POCD is neuroinflammation induced by microglia. Resveratrol has emerged as a promising candidate for the prevention of cognitive decline. Previous studies have demonstrated its potential in alleviating cognitive deterioration, yielding encouraging results. Nonetheless, the mechanism of resveratrol improving cognitive function remains unclear. Therefore, we assessed the effect of resveratrol in both aged POCD model mice and BV2 cells on CX3CL1/CX3CR1 axis, a critical signaling pathway mediating microglial activity. Both in vitro and in vivo experiments have revealed that pre-administration of resveratrol not only mitigates cognitive deficits but also significantly reduces the levels of inflammatory cytokines. Additionally, it enhanced the expression of SIRT1 and CX3CR1 within the hippocampal region. We also evaluated the impact of resveratrol on CX3CR1 siRNA transfected BV2 cells. Delete of CX3CR1 reversed the preventive role of resveratrol. Our findings implied that resveratrol might inhibit microglial activation and improve cognition by mediating CX3CL1/CX3CR1 signaling.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138089"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882554","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":"Thalamo-insular cortex connections in the rat and human","authors":"Mazhar Özkan ,&nbsp;Damlasu Altınöz ,&nbsp;Elif Erkan ,&nbsp;Yasin Celal Güneş ,&nbsp;Oktay Algın ,&nbsp;Safiye Çavdar","doi":"10.1016/j.neulet.2024.138111","DOIUrl":"10.1016/j.neulet.2024.138111","url":null,"abstract":"<div><div>The insular cortex (ICx) has a role in large a variety of functions. Thalamus plays an important role in modulating cortical functions. The present study aims to show thalamic-ICx connections using the fluoro-gold (FG) tracing method in rats and diffusion tensoring-based tractography (DTI) in humans. Wistar albino rats were pressure injected with the FG tracer into the anterior and posterior ICx. The DTI data were obtained from the Human Connectome Project database. Our findings showed that the thalamic-ICx connections were strictly ipsilateral in the rat, however, bilateral connections were present in humans. The anterior ICx was connected to the paraventricular, centromedial, paracentral, centrolateral, ventral posteromedial, and medial geniculate thalamic nuclei. The posterior ICx was connected to the centromedian, parafasicular, renuence, lateral, posterior, ventral posteromedial, and medial geniculate thalamic nuclei. The DTI in humans corresponded with the results of the experimental study on rats. The results of the current study may provide an understanding of how thalamic nuclei may contribute to higher-order ICx functions. The ipsilateral connections in the rat and bilateral in humans may provide insights into anatomical evolution and functional differences of the ICx circuit in humans and rats. Further, stimulation of the thalamus can be a potential target for treating or modulating ICx functions such as anxiety, depression, and certain chronic pain conditions.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138111"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922184","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":"Dopamine D2 receptor antagonists alter autophosphorylation of focal adhesion kinases in the mouse forebrain in vivo","authors":"Li-Min Mao ,&nbsp;Tayyibah Mahmood ,&nbsp;John Q. Wang","doi":"10.1016/j.neulet.2025.138145","DOIUrl":"10.1016/j.neulet.2025.138145","url":null,"abstract":"<div><div>Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase expressed in neurons of the developing and adult brain in addition to non-neuronal cells. Activation of FAK is initiated by autophosphorylation of the kinase at tyrosine 397 (Y397). Active FAK transmits extracellular signals inside neurons to integrate cytoskeletal rearrangements and modulate synaptic transmission and plasticity. Here we investigated roles of dopamine receptors, i.e., G_αs/olf-coupled D₁ and G_αi/o-coupled D₂ subtypes, in regulation of FAK autophosphorylation in two major dopamine-innervated areas of the mouse brain <em>in vivo</em>. We found that acute systemic administration of a dopamine D₁ or D₂ receptor agonist had no effect on basal FAK autophosphorylation at Y397 in the striatum and medial prefrontal cortex (mPFC). Similarly, a D₁ receptor antagonist did not alter striatal and cortical Y397 phosphorylation. However, acute injection of a D₂ receptor antagonist (eticlopride or haloperidol) induced a marked increase in Y397 phosphorylation in the striatum and mPFC. The eticlopride-induced Y397 phosphorylation can be seen in the two striatal subdivisions, the caudate putamen and nucleus accumbens, and was induced at two effective doses (0.1 and 0.5 mg/kg). All drug treatments caused insignificant changes in cellular FAK protein expression. These results reveal an existence of a tonic inhibitory tone of dopamine D₂ receptors over basal FAK autophosphorylation in the mouse striatum and mPFC.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138145"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080727","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":"Unveiling encephalopathy signatures: A deep learning approach with locality-preserving features and hybrid neural network for EEG analysis","authors":"Jisu Elsa Jacob ,&nbsp;Sreejith Chandrasekharan ,&nbsp;Thomas Iype ,&nbsp;Ajith Cherian","doi":"10.1016/j.neulet.2025.138146","DOIUrl":"10.1016/j.neulet.2025.138146","url":null,"abstract":"<div><div>EEG signals exhibit spatio-temporal characteristics due to the neural activity dispersion in space over the brain and the dynamic temporal patterns of electrical activity in neurons. This study tries to effectively utilize the spatio-temporal nature of EEG signals for diagnosing encephalopathy using a combination of novel locality preserving feature extraction using Local Binary Patterns (LBP) and a custom fine-tuned Long Short-Term Memory (LSTM) neural network. A carefully curated primary EEG dataset is used to assess the effectiveness of the technique for treatment of encephalopathies. EEG signals of all electrodes are mapped onto a spatial matrix from which the custom feature extraction method isolates spatial features of the signals. These spatial features are further given to the neural network, which learns to combine the spatial information with temporal dynamics summarizing pertinent details from the raw EEG data. Such a unified representation is key to perform reliable disease classification at the output layer of the neural network, leading to a robust classification system, potentially providing improved diagnosis and treatment. The proposed method shows promising potential for enhancing the automated diagnosis of encephalopathy, with a remarkable accuracy rate of 90.5%. To the best of our knowledge, this is the first attempt to compress and represent both spatial and temporal features into a single vector for encephalopathy detection, simplifying visual diagnosis and providing a robust feature for automated predictions. This advancement holds significant promise for ensuring early detection and intervention strategies in the clinical environment, which in turn enhances patient care.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138146"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080692","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}