Brain communications最新文献

{"title":"A novel tauopathy model mimicking molecular and spatial aspects of human tau pathology.","authors":"Rin Yanai, Tomoki T Mitani, Etsuo A Susaki, Takeharu Minamihisamatsu, Masafumi Shimojo, Yuri Saito, Hiroshi Mizuma, Nobuhiro Nitta, Daita Kaneda, Yoshio Hashizume, Gen Matsumoto, Kentaro Tanemura, Ming-Rong Zhang, Makoto Higuchi, Hiroki R Ueda, Naruhiko Sahara","doi":"10.1093/braincomms/fcae326","DOIUrl":"https://doi.org/10.1093/braincomms/fcae326","url":null,"abstract":"<p><p>Creating a mouse model that recapitulates human tau pathology is essential for developing strategies to intervene in tau-induced neurodegeneration. However, mimicking the pathological features seen in human pathology often involves a trade-off with artificial effects such as unexpected gene insertion and neurotoxicity from the expression system. To overcome these issues, we developed the rTKhomo mouse model by combining a transgenic CaMKII-tTA system with a P301L mutated 1N4R human tau knock-in at the <i>Rosa26</i> locus with a C57BL/6J background. This model closely mimics human tau pathology, particularly in the hippocampal CA1 region, showing age-dependent tau accumulation, neuronal loss and neuroinflammation. Notably, whole-brain 3D staining and light-sheet microscopy revealed a spatial gradient of tau deposition from the entorhinal cortex to the hippocampus, similar to the spatial distribution of Braak neurofibrillary tangle staging. Furthermore, [¹⁸F]PM-PBB3 positron emission tomography imaging enabled the quantification and live monitoring of tau deposition. The rTKhomo mouse model shows potential as a promising next-generation preclinical tool for exploring the mechanisms of tauopathy and for developing interventions targeting the spatial progression of tau pathology.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae326"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related differences in human cortical microstructure depend on the distance to the nearest vein.","authors":"Christoph Knoll, Juliane Doehler, Alicia Northall, Stefanie Schreiber, Johanna Rotta, Hendrik Mattern, Esther Kuehn","doi":"10.1093/braincomms/fcae321","DOIUrl":"10.1093/braincomms/fcae321","url":null,"abstract":"<p><p>Age-related differences in cortical microstructure are used to understand the neuronal mechanisms that underlie human brain ageing. The cerebral vasculature contributes to cortical ageing, but its precise interaction with cortical microstructure is poorly understood. In a cross-sectional study, we combine venous imaging with vessel distance mapping to investigate the interaction between venous distances and age-related differences in the microstructural architecture of the primary somatosensory cortex, the primary motor cortex and additional areas in the frontal cortex as non-sensorimotor control regions. We scanned 18 younger adults and 17 older adults using 7 Tesla MRI to measure age-related changes in longitudinal relaxation time (T1) and quantitative susceptibility mapping (QSM) values at 0.5 mm isotropic resolution. We modelled different cortical depths using an equi-volume approach and assessed the distance of each voxel to its nearest vein using vessel distance mapping. Our data reveal a dependence of cortical quantitative T1 values and positive QSM values on venous distance. In addition, there is an interaction between venous distance and age on quantitative T1 values, driven by lower quantitative T1 values in older compared to younger adults in voxels that are closer to a vein. Together, our data show that the local venous architecture explains a significant amount of variance in standard measures of cortical microstructure and should be considered in neurobiological models of human brain organisation and cortical ageing.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae321"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between changes in functional connectivity gradients and cognitive-emotional disorders in sudden sensorineural hearing loss.","authors":"Biao Li, Xiao-Min Xu, Yuan-Qing Wu, Xiu-Qian Miao, Yuan Feng, Yu-Chen Chen, Richard Salvi, Jin-Jing Xu, Jian-Wei Qi","doi":"10.1093/braincomms/fcae317","DOIUrl":"https://doi.org/10.1093/braincomms/fcae317","url":null,"abstract":"<p><p>Sudden sensorineural hearing loss, a prevalent emergency in otolaryngology, is known to potentially precipitate cognitive and emotional disorders in affected individuals. Extensive research has documented the phenomenon of cortical functional reorganization in patients with sudden sensorineural hearing loss. However, the potential link between this neural functional remodelling and cognitive-emotional disorders remains unclear. To investigate this issue, 30 bilateral sudden sensorineural hearing loss patients and 30 healthy adults were recruited for this study. We collected clinical data and resting-state functional magnetic resonance imaging data from the participants. Gradient mapping analysis was employed to calculate the first three gradients for each subject. Subsequently, gradient changes in sudden sensorineural hearing loss patients were compared with healthy controls at global, regional and network levels. Finally, we explored the relationship between gradient values and clinical variables. The results revealed that at the global level, sudden sensorineural hearing loss did not exhibit significant differences in the primary gradient but showed a state of compression in the second and third gradients. At the regional level, sudden sensorineural hearing loss patients exhibited a significant reduction in the primary gradient values in the temporal pole and ventral prefrontal cortex, which were closely related to neuro-scale scores. Regarding the network level, sudden sensorineural hearing loss did not show significant differences in the primary gradient but instead displayed significant changes in the control network and default mode network in the second and third gradients. This study revealed disruptions in the functional hierarchy of sudden sensorineural hearing loss, and the alterations in functional connectivity gradients were closely associated with cognitive and emotional disturbances in patients. These findings provide new evidence for understanding the functional remodelling that occurs in sudden sensorineural hearing loss.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae317"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy.","authors":"Marson Putra, Nikhil S Rao, Cara Gardner, Guanghao Liu, Jordan Trommater, Michael Bunney, Meghan Gage, Alexander G Bassuk, Marco Hefti, Gloria Lee, Thimmasettappa Thippeswamy","doi":"10.1093/braincomms/fcae327","DOIUrl":"10.1093/braincomms/fcae327","url":null,"abstract":"<p><p>Epilepsy and Alzheimer's disease share some common pathologies such as neurodegeneration, seizures and impaired cognition. However, the molecular mechanisms of these changes are still largely unknown. Fyn, a Src-family non-receptor tyrosine kinase (SFK), and its interaction with tau in mediating brain pathology in epilepsy and Alzheimer's disease can be a potential therapeutic target for disease modification. Although Fyn and tau pathology occurs in both Alzheimer's disease and epilepsy, the dynamics of Fyn-tau and PSD95-NR2B interactions affected by seizures and their impact on brain pathology in epilepsy have not been investigated. In this study, we demonstrate a significant increase of Fyn-tau interactions following seizure induction by kainate in both acute and chronic rodent models and in human epilepsy. In the early phase of epileptogenesis, we show increased Fyn/tau/NR2B/PSD95/neuronal nitric oxide synthase complexes after status epilepticus and a postsynaptic increase of phosphorylated tau (pY18 and AT8), Fyn (pSFK-Y416), NMDAR (pNR2B-Y1472) and neuronal nitric oxide synthase. Hippocampal proximity ligation assay and co-immunoprecipitation revealed a sustained increase of Fyn-tau and NR2B-PSD95 complexes/binding in rat chronic epilepsy at 3 months post-status epilepticus. Enhanced Fyn-tau complexes strongly correlated with the frequency of spontaneously recurring convulsive seizures and epileptiform spikes in the chronic epilepsy model. In human epileptic brains, we also identified increased Fyn-tau and NR2B-PSD95 complexes, tau phosphorylation (pY18 and AT8) and Fyn activation (pSFK-Y416), implying the translational and therapeutic potential of these molecular interactions. In <i>tau</i> knockout mice and in rats treated with a Fyn/SFK inhibitor saracatinib, we found a significant reduction of phosphorylated Fyn, tau (AT8 in saracatinib-treated), NR2B and neuronal nitric oxide synthase and their interactions (Fyn-tau and NR2B-PSD95 in saracatinib-treated group; NR2B-PSD95 in <i>tau</i> knockout group). The reduction of Fyn-tau and NR2B-PSD95 interactions in the saracatinib-treated group, in contrast to the vehicle-treated group, correlated with the modification in seizure progression in the rat chronic epilepsy model. These findings from animal models and human epilepsy provide evidence for the role of Fyn-tau and NR2B-PSD95 interactions in seizure-induced brain pathology and suggest that blocking such interactions could modify the progression of epilepsy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae327"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent delirium is associated with cerebrospinal fluid markers of neuronal injury.","authors":"Alex Tsui, Benjamin Johnstone, Amanda Heslegrave, Henrik Zetterberg, Leiv Otto Watne, Bjørn Erik Neerland, Maria Krogseth, Colm Cunningham, Alasdair MacLullich, Graciela Muniz Terrera, Daniel Davis, Gideon Caplan","doi":"10.1093/braincomms/fcae319","DOIUrl":"10.1093/braincomms/fcae319","url":null,"abstract":"<p><p>Delirium is associated with the risk of future long-term cognitive impairment, but the degree to which markers of neuronal injury may be distinct or shared with dementia has yet to be comprehensively described. We investigated CSF biomarkers of dementia, astrocytosis and neuronal damage in a clinical cohort with persistent delirium, comparing them with an outpatient memory clinic sample. Our aim was to determine if different patterns of biomarker changes could implicate specific mechanisms for delirium-related neuronal injury over and above that attributable to comorbid dementia. We recruited 35 participants from the Prince of Wales Hospital, Sydney, Australia. We included inpatients with delirium persisting for at least 5 days (<i>n</i> = 15, 10 with underlying dementia) and participants from outpatient memory clinics (<i>n</i> = 20, 17 with dementia). CSF assays were as follows: amyloid-β₄₂, amyloid-β₄₀, phosphorylated tau181, neurofilament light chain and glial fibrillary acidic protein. We used propensity score matching to estimate effect sizes for each standardized CSF biomarker separately for persistent delirium (irrespective of underlying dementia) and dementia (irrespective of superimposed delirium). Compared with individuals without delirium, persistent delirium was associated with elevated glial fibrillary acidic protein (normalized coefficient per transformed standard deviation, <i>β</i> = 0.85; 95% confidence interval: 0.03-1.68) and neurofilament light chain (<i>β</i> = 1.1; 95% confidence interval: 0.5-1.6), but not phosphorylated tau181. Compared with individuals without dementia, glial fibrillary acidic protein, neurofilament light chain and phosphorylated tau181 were all increased to expected levels in dementia cases, with the former two biomarkers at levels comparable to those seen in persistent delirium [glial fibrillary acidic protein (<i>β</i> = 1.54; 95% confidence interval: 1.05-2.0) and neurofilament light chain (<i>β</i> = 0.65; 95% confidence interval: 0.24-1.1)]. Persistent delirium was linked with changes in CSF biomarkers not necessarily attributable to dementia. These findings support the potential that delirium is associated with direct neuronal injury independent of dementia pathophysiology. Whether this neuronal injury involves astrocyte dysfunction or direct axonal damage are both possibilities. Future work examining acute brain injury in delirium is needed.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae319"},"PeriodicalIF":4.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Children born very preterm experience altered cortical expansion over the first decade of life.","authors":"Lisa S Gorham, Aidan R Latham, Dimitrios Alexopoulos, Jeanette K Kenley, Emily Iannopollo, Rachel E Lean, David Loseille, Tara A Smyser, Jeffrey J Neil, Cynthia E Rogers, Christopher D Smyser, Kara Garcia","doi":"10.1093/braincomms/fcae318","DOIUrl":"10.1093/braincomms/fcae318","url":null,"abstract":"<p><p>The brain develops rapidly from the final trimester of gestation through childhood, with cortical surface area expanding greatly in the first decade of life. However, it is unclear exactly where and how cortical surface area changes after birth, or how prematurity affects these developmental trajectories. Fifty-two very preterm (gestational age at birth = 26 ± 1.6 weeks) and 41 full-term (gestational age at birth = 39 ± 1.2 weeks) infants were scanned using structural magnetic resonance imaging at term-equivalent age and again at 9/10 years of age. Individual cortical surface reconstructions were extracted for each scan. Infant and 9/10 cortical surfaces were aligned using anatomically constrained Multimodal Surface Matching (aMSM), a technique that allows calculation of local expansion gradients across the cortical surface for each individual subject. At the neonatal time point, very preterm infants had significantly smaller surface area than their full-term peers (<i>P</i> < 0.001), but at the age 9/10-year time point, very preterm and full-term children had comparable surface area (<i>P</i> > 0.05). Across all subjects, cortical expansion by age 9/10 years was most pronounced in frontal, temporal, and supramarginal/inferior parietal junction areas, which are key association cortices (<i>P</i> _Spin < 0.001). Very preterm children showed greater cortical surface area expansion between term-equivalent age and age 9/10 compared to their full-term peers in the medial and lateral frontal areas, precuneus, and middle temporal/banks of the superior sulcus junction (<i>P</i> < 0.05). Furthermore, within the very preterm group, expansion was highly variable within the orbitofrontal cortex and posterior regions of the brain. By mapping these patterns across the cortex, we identify differences in association cortices that are known to be important for executive functioning, emotion processing, and social cognition. Additional longitudinal work will be needed to understand if increased expansion in very preterm children is adaptive, or if differences persist into adulthood.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae318"},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifetime history of head injury is associated with reduced perivascular space number in acute mild traumatic brain injury.","authors":"Kiersten J Garcia, Grace Brolly, Daniel Ng, Maria Bederson, Pedro Martinez, Mark D Whiting","doi":"10.1093/braincomms/fcae314","DOIUrl":"https://doi.org/10.1093/braincomms/fcae314","url":null,"abstract":"<p><p>Traumatic brain injury impairs function of the glymphatic system, a perivascular network involved in waste clearance. Enlarged perivascular spaces visible on MRI are an emerging biomarker of glymphatic function. This study characterized enlarged perivascular spaces in acute head injury with 7 T MRI. Healthy controls (<i>n</i> = 8) and patients (<i>n</i> = 11) with mild traumatic brain injury underwent MRI within 7 days of injury and were evaluated for lifetime history of head injury, neurobehavioral symptoms and sleep disturbances. MRI-visible perivascular spaces were quantified and assessed according to published criteria. The number of enlarged perivascular spaces was significantly higher in traumatic brain injury patients than controls (<i>P</i> = 0.015). Among healthy controls, 6/8 scored 'none' or 'mild' on the perivascular space rating scale, while 10/11 patients scored 'moderate', 'frequent' or 'severe'. There was an inverse relationship between perivascular space number and number of lifetime head injuries. Patients with more prior head injuries exhibited fewer enlarged perivascular spaces (<i>P</i> = 0.014). These results indicate that mild head injury results in acute alterations in perivascular space number, and this effect is mediated by previous head injury history. Enlarged perivascular spaces may reflect a glymphatic response that is diminished after multiple head injuries, although this will require further study.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae314"},"PeriodicalIF":4.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain anticipation is a new behavioural sign of minimally conscious state.","authors":"Aude Sangare, Esteban Munoz-Musat, Amina Ben Salah, Melanie Valente, Clemence Marois, Sophie Demeret, Jacobo Diego Sitt, Benjamin Rohaut, Lionel Naccache","doi":"10.1093/braincomms/fcae311","DOIUrl":"https://doi.org/10.1093/braincomms/fcae311","url":null,"abstract":"<p><p>Probing cognition and consciousness in the absence of functional communication remains an extremely challenging task. In this perspective, we imagined a basic clinical procedure to explore pain anticipation at bedside. In a series of 61 patients with a disorder of consciousness, we tested the existence of a nociceptive anticipation response by pairing a somaesthetic stimulation with a noxious stimulation. We then explored how nociceptive anticipation response correlated with (i) clinical status inferred from Coma Recovery Scale-Revised scoring, (ii) with an EEG signature of stimulus anticipation-the contingent negative variation-and (iii) how nociceptive anticipation response could predict consciousness outcome at 6 months. Proportion of nociceptive anticipation response differed significantly according to the state of consciousness: nociceptive anticipation response was present in 5 of 5 emerging from minimally conscious state patients (100%), in 10 of 11 minimally conscious state plus patients (91%), but only in 8 of 17 minimally conscious state minus patients (47%), and only in 1 of 24 vegetative state/unresponsive wakefulness syndrome patients (4%) (<i>χ</i> ²  <i>P</i> < 0.0001). Nociceptive anticipation response correlated with the presence of a contingent negative variation, suggesting that patients with nociceptive anticipation response were more prone to actively expect and anticipate auditory stimuli (Fisher's exact test <i>P</i> = 0.05). However, nociceptive anticipation response presence did not predict consciousness recovery. Nociceptive anticipation response appears as a new additional behavioural sign that can be used to differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome patients. As most behavioural signs of minimally conscious state, the nociceptive anticipation response seems to reveal the existence of a cortically mediated state that does not necessarily reflect residual conscious processing.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae311"},"PeriodicalIF":4.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD8 positive T-cells decrease neurogenesis and induce anxiety-like behaviour following hepatitis B vaccination.","authors":"Tuo Zhou, Yuxuan Gao, Zhiling Wang, Chunfang Dai, Ming Lei, Aubrey Liew, Sen Yan, Zhibin Yao, Dandan Hu, Fangfang Qi","doi":"10.1093/braincomms/fcae315","DOIUrl":"10.1093/braincomms/fcae315","url":null,"abstract":"<p><p>Mounting evidence indicates the involvement of peripheral immunity in the regulation of brain function, influencing aspects such as neuronal development, emotion, and cognitive abilities. Previous studies from our laboratory have revealed that neonatal hepatitis B vaccination can downregulate hippocampal neurogenesis, synaptic plasticity and spatial learning memory. In the current post-epidemic era characterized by universal vaccination, understanding the impact of acquired immunity on neuronal function and neuropsychiatric disorders, along with exploring potential underlying mechanisms, becomes imperative. We employed hepatitis B vaccine-induced CD3 positive T cells in immunodeficient mice to investigate the key mechanisms through which T cell subsets modulate hippocampal neurogenesis and anxiety-like behaviours. Our data revealed that mice receiving hepatitis B vaccine-induced T cells exhibited heightened anxiety and decreased hippocampal cell proliferation compared to those receiving phosphate-buffered saline-T cells or wild-type mice. Importantly, these changes were predominantly mediated by infiltrated CD8⁺ T cells into the brain, rather than CD4⁺ T cells. Transcriptome profiling of CD8⁺ T cells unveiled that C-X-C motif chemokine receptor 6 positive (CXCR6⁺) CD8⁺ T cells were recruited into the brain through microglial and astrocyte-derived C-X-C motif chemokine ligand 16 (CXCL16). This recruitment process impaired neurogenesis and induced anxiety-like behaviour via tumour necrosis factor-α-dependent mechanisms. Our findings highlight the role of glial cell derived CXCL16 in mediating the recruitment of CXCR6⁺CD8⁺ T cell subsets into the brain. This mechanism represents a potential avenue for modulating hippocampal neurogenesis and emotion-related behaviours after hepatitis B vaccination.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae315"},"PeriodicalIF":4.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A microRNA diagnostic biomarker for amyotrophic lateral sclerosis.","authors":"Sandra Anne Banack, Rachael A Dunlop, Paul Mehta, Hiroshi Mitsumoto, Stewart P Wood, Moon Han, Paul Alan Cox","doi":"10.1093/braincomms/fcae268","DOIUrl":"https://doi.org/10.1093/braincomms/fcae268","url":null,"abstract":"<p><p>Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific. Extracellular vesicles were extracted from blood plasma obtained from individuals diagnosed with amyotrophic lateral sclerosis, primary lateral sclerosis, Parkinson's disease and healthy controls. Immunoaffinity purification was used to create a neural-enriched extracellular vesicle fraction. MicroRNAs were measured across sample cohorts using real-time polymerase chain reaction. A Kruskal-Wallis test was used to assess differences in plasma microRNAs followed by <i>post hoc</i> Mann-Whitney tests to compare disease groups. Diagnostic accuracy was determined using a machine learning algorithm and a logistic regression model. We identified an eight-microRNA diagnostic signature for blood samples from amyotrophic lateral sclerosis patients with high sensitivity and specificity and an area under the curve calculation of 98% with clear statistical separation from neurological controls. The eight identified microRNAs represent disease-related biological processes consistent with amyotrophic lateral sclerosis. The direction and magnitude of gene fold regulation are consistent across four separate patient cohorts with real-time polymerase chain reaction analyses conducted in two laboratories from diverse samples and sample collection procedures. We propose that this diagnostic signature could be an aid to neurologists to supplement current clinical metrics used to diagnose amyotrophic lateral sclerosis.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"6 5","pages":"fcae268"},"PeriodicalIF":4.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11398878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}