BMC Neuroscience最新文献

{"title":"Cardiovascular history and risk of idiopathic Parkinson's disease: a cross-sectional observational study.","authors":"Shubhra Acharya, Andrew I Lumley, Yvan Devaux","doi":"10.1186/s12868-024-00875-y","DOIUrl":"10.1186/s12868-024-00875-y","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD), while often associated with its distinctive motor symptoms, can also exert a notable impact on the cardiovascular system due to the development of severe autonomic dysfunction. One of the initial indicators of PD is the appearance of cardiovascular dysautonomia. As such, it is vital to monitor and manage cardiovascular health of individuals with PD, as it may have clinical implications in the development of commonly recognized motor and non-motor aspects of the disease. To study the association of history of cardiovascular disease (CVD) with occurrence and severity of PD, here, we lend data on the association of CVD history with the frequency and the occurrence of idiopathic PD (iPD) using data from the Luxembourg Parkinson's study (iPD n = 676 patients and non-PD n = 874 controls).</p><p><strong>Results: </strong>We report that patients with a history of CVD are at high risk of developing iPD (odds ratio; OR = 1.56, 95% confidence interval; CI 1.09-2.08). This risk is stronger in males and remains significant after adjustment with confounders (OR 1.55, 95% CI 1.05-2.30). This increased susceptibility to iPD is linked to the severity of iPD symptoms mainly the non-motor symptoms of daily living (MDS-UPDRS I) and motor complications (MDS-UPDRS IV) in the affected individuals.</p><p><strong>Conclusion: </strong>Individuals with history of CVD have a high risk of developing severe forms of iPD. This observation suggests that careful monitoring and management of patients with a history of cardiac problems may reduce the burden of iPD.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"33"},"PeriodicalIF":2.4,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558027","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":"Simulated complexes formed from a set of postsynaptic proteins suggest a localised effect of a hypomorphic Shank mutation.","authors":"Marcell Miski, Áron Weber, Krisztina Fekete-Molnár, Bence Márk Keömley-Horváth, Attila Csikász-Nagy, Zoltán Gáspári","doi":"10.1186/s12868-024-00880-1","DOIUrl":"10.1186/s12868-024-00880-1","url":null,"abstract":"<p><strong>Background: </strong>The postsynaptic density is an elaborate protein network beneath the postsynaptic membrane involved in the molecular processes underlying learning and memory. The postsynaptic density is built up from the same major proteins but its exact composition and organization differs between synapses. Mutations perturbing protein: protein interactions generally occurring in this network might lead to effects specific for cell types or processes, the understanding of which can be especially challenging.</p><p><strong>Results: </strong>In this work we use systems biology-based modeling of protein complex distributions in a simplified set of major postsynaptic proteins to investigate the effect of a hypomorphic Shank mutation perturbing a single well-defined interaction. We use data sets with widely variable abundances of the constituent proteins. Our results suggest that the effect of the mutation is heavily dependent on the overall availability of all the protein components of the whole network and no trivial correspondence between the expression level of the directly affected proteins and overall complex distribution can be observed.</p><p><strong>Conclusions: </strong>Our results stress the importance of context-dependent interpretation of mutations. Even the weakening of a generally occurring protein: protein interaction might have well-defined effects, and these can not easily be predicted based only on the abundance of the proteins directly affected. Our results provide insight on how cell-specific effects can be exerted by a mutation perturbing a generally occurring interaction even when the wider interaction network is largely similar.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"32"},"PeriodicalIF":2.4,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544512","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":"Changes of brain functional network in Alzheimer's disease and frontotemporal dementia: a graph-theoretic analysis.","authors":"Shijing Wu, Ping Zhan, Guojing Wang, Xiaohua Yu, Hongyun Liu, Weidong Wang","doi":"10.1186/s12868-024-00877-w","DOIUrl":"10.1186/s12868-024-00877-w","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias, presenting with similar clinical features that challenge accurate diagnosis. Despite extensive research, the underlying pathophysiological mechanisms remain unclear, and effective treatments are limited. This study aims to investigate the alterations in brain network connectivity associated with AD and FTD to enhance our understanding of their pathophysiology and establish a scientific foundation for their diagnosis and treatment.</p><p><strong>Methods: </strong>We analyzed preprocessed electroencephalogram (EEG) data from the OpenNeuro public dataset, comprising 36 patients with AD, 23 patients with FTD, and 29 healthy controls (HC). Participants were in a resting state with eyes closed. We estimated the average functional connectivity using the Phase Lag Index (PLI) for lower frequencies (delta and theta) and the Amplitude Envelope Correlation with leakage correction (AEC-c) for higher frequencies (alpha, beta, and gamma). Graph theory was applied to calculate topological parameters, including mean node degree, clustering coefficient, characteristic path length, global and local efficiency. A permutation test was then utilized to assess changes in brain network connectivity in AD and FTD based on these parameters.</p><p><strong>Results: </strong>Both AD and FTD patients showed increased mean PLI values in the theta frequency band, along with increases in average node degree, clustering coefficient, global efficiency, and local efficiency. Conversely, mean AEC-c values in the alpha frequency band were notably diminished, which was accompanied by decreases average node degree, clustering coefficient, global efficiency, and local efficiency. Furthermore, AD patients in the occipital region showed an increase in theta band node degree and decreased alpha band clustering coefficient and local efficiency, a pattern not observed in FTD.</p><p><strong>Conclusions: </strong>Our findings reveal distinct abnormalities in the functional network topology and connectivity in AD and FTD, which may contribute to a better understanding of the pathophysiological mechanisms of these diseases. Specifically, patients with AD demonstrated a more widespread change in functional connectivity, while those with FTD retained connectivity in the occipital lobe. These observations could provide valuable insights for developing electrophysiological markers to differentiate between the two diseases.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"30"},"PeriodicalIF":2.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533554","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":"Persistent vocal learning in an aging open-ended learner reflected in neural FoxP2 expression.","authors":"Bushra Moussaoui, Kennedy Ulmer, Marcelo Araya-Salas, Timothy F Wright","doi":"10.1186/s12868-024-00879-8","DOIUrl":"10.1186/s12868-024-00879-8","url":null,"abstract":"<p><strong>Background: </strong>Most vocal learning species exhibit an early critical period during which their vocal control neural circuitry facilitates the acquisition of new vocalizations. Some taxa, most notably humans and parrots, retain some degree of neurobehavioral plasticity throughout adulthood, but both the extent of this plasticity and the neurogenetic mechanisms underlying it remain unclear. Differential expression of the transcription factor FoxP2 in both songbird and parrot vocal control nuclei has been identified previously as a key pattern facilitating vocal learning. We hypothesize that the resilience of vocal learning to cognitive decline in open-ended learners will be reflected in an absence of age-related changes in neural FoxP2 expression. We tested this hypothesis in the budgerigar (Melopsittacus undulatus), a small gregarious parrot in which adults converge on shared call types in response to shifts in group membership. We formed novel flocks of 4 previously unfamiliar males belonging to the same age class, either \"young adult\" (6 mo - 1 year) or \"older adult\" (≥ 3 year), and then collected audio-recordings over a 20-day learning period to assess vocal learning ability. Following behavioral recording, immunohistochemistry was performed on collected neural tissue to measure FoxP2 protein expression in a parrot vocal learning center, the magnocellular nucleus of the medial striatum (MMSt), and its adjacent striatum.</p><p><strong>Results: </strong>Although older adults show lower vocal diversity (i.e. repertoire size) and higher absolute levels of FoxP2 in the MMSt than young adults, we find similarly persistent downregulation of FoxP2 and equivalent vocal plasticity and vocal convergence in the two age cohorts. No relationship between individual variation in vocal learning measures and FoxP2 expression was detected.</p><p><strong>Conclusions: </strong>We find neural evidence to support persistent vocal learning in the budgerigar, suggesting resilience to aging in the open-ended learning program of this species. The lack of a significant relationship between FoxP2 expression and individual variability in vocal learning performance suggests that other neurogenetic mechanisms could also regulate this complex behavior.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"31"},"PeriodicalIF":2.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533484","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":"The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke.","authors":"Daniel Navin Olschewski, Nilufar Nazarzadeh, Felix Lange, Anna Maria Koenig, Christina Kulka, Jella-Andrea Abraham, Stefan Johannes Blaschke, Rudolf Merkel, Bernd Hoffmann, Gereon Rudolf Fink, Michael Schroeter, Maria Adele Rueger, Sabine Ulrike Vay","doi":"10.1186/s12868-024-00876-x","DOIUrl":"10.1186/s12868-024-00876-x","url":null,"abstract":"<p><strong>Background: </strong>Astrocytes are the most abundant cell type of the central nervous system and are fundamentally involved in homeostasis, neuroprotection, and synaptic plasticity. This regulatory function of astrocytes on their neighboring cells in the healthy brain is subject of current research. In the ischemic brain we assume disease specific differences in astrocytic acting. The renin-angiotensin-aldosterone system regulates arterial blood pressure through endothelial cells and perivascular musculature. Moreover, astrocytes express angiotensin II type 1 and 2 receptors. However, their role in astrocytic function has not yet been fully elucidated. We hypothesized that the angiotensin II receptors impact astrocyte function as revealed in an in vitro system mimicking cerebral ischemia. Astrocytes derived from neonatal wistar rats were exposed to telmisartan (angiotensin II type 1 receptor-blocker) or PD123319 (angiotensin II type 2 receptor-blocker) under normal conditions (control) or deprivation from oxygen and glucose. Conditioned medium (CM) of astrocytes was harvested to elucidate astrocyte-mediated indirect effects on microglia and cortical neurons.</p><p><strong>Result: </strong>The blockade of angiotensin II type 1 receptor by telmisartan increased the survival of astrocytes during ischemic conditions in vitro without affecting their proliferation rate or disturbing their expression of S100A10, a marker of activation. The inhibition of the angiotensin II type 2 receptor pathway by PD123319 resulted in both increased expression of S100A10 and proliferation rate. The CM of telmisartan-treated astrocytes reduced the expression of pro-inflammatory mediators with simultaneous increase of anti-inflammatory markers in microglia. Increased neuronal activity was observed after treatment of neurons with CM of telmisartan- as well as PD123319-stimulated astrocytes.</p><p><strong>Conclusion: </strong>Data show that angiotensin II receptors have functional relevance for astrocytes that differs in healthy and ischemic conditions and effects surrounding microglia and neuronal activity via secretory signals. Above that, this work emphasizes the strong interference of the different cells in the CNS and that targeting astrocytes might serve as a therapeutic strategy to influence the acting of glia-neuronal network in de- and regenerative context.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"29"},"PeriodicalIF":2.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11202395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455222","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":"Diabetes mellitus and risk of incident dementia in APOE ɛ4 carriers: an updated meta-analysis.","authors":"Ava Rashtchian, Mohammad Hossein Etemadi, Elham Asadi, Sara Binaei, Mina Abbasi, Maedeh Bayani, Erfan Izadi, Sayedeh-Fatemeh Sadat-Madani, Mahdyieh Naziri, Sahar Khoshravesh, Mahsa Shirani, Mahsa Asadi Anar, Niloofar Deravi","doi":"10.1186/s12868-024-00878-9","DOIUrl":"10.1186/s12868-024-00878-9","url":null,"abstract":"<p><strong>Background and aim: </strong>Diabetes raises the risk of dementia, mortality, and cognitive decline in the elderly, potentially because of hereditary variables such as APOE. In this study, we aim to evaluate Diabetes mellitus and the risk of incident dementia in APOE ɛ4 carriers.</p><p><strong>Method: </strong>We thoroughly searched PubMed (Medline), Scopus, and Google Scholar databases for related articles up to September 2023. The titles, abstracts, and full texts of articles were reviewed; data were extracted and analyzed.</p><p><strong>Result: </strong>This meta-analysis included nine cohorts and seven cross-sectional articles with a total of 42,390 population. The study found that APOE ɛ4 carriers with type 2 diabetes (T2D) had a 48% higher risk of developing dementia compared to non-diabetic carriers (Hazard Ratio;1.48, 95%CI1.36-1.60). The frequency of dementia was 3 in 10 people (frequency: 0.3; 95%CI (0.15-0.48). No significant heterogeneity was observed. Egger's test, which we performed, revealed no indication of publication bias among the included articles (p = 0.2).</p><p><strong>Conclusion: </strong>Overall, diabetes increases the risk of dementia, but further large-scale studies are still required to support the results of current research.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"28"},"PeriodicalIF":2.4,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11201872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449596","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":"Autism spectrum disorders detection based on multi-task transformer neural network.","authors":"Le Gao, Zhimin Wang, Yun Long, Xin Zhang, Hexing Su, Yong Yu, Jin Hong","doi":"10.1186/s12868-024-00870-3","DOIUrl":"10.1186/s12868-024-00870-3","url":null,"abstract":"<p><p>Autism Spectrum Disorders (ASD) are neurodevelopmental disorders that cause people difficulties in social interaction and communication. Identifying ASD patients based on resting-state functional magnetic resonance imaging (rs-fMRI) data is a promising diagnostic tool, but challenging due to the complex and unclear etiology of autism. And it is difficult to effectively identify ASD patients with a single data source (single task). Therefore, to address this challenge, we propose a novel multi-task learning framework for ASD identification based on rs-fMRI data, which can leverage useful information from multiple related tasks to improve the generalization performance of the model. Meanwhile, we adopt an attention mechanism to extract ASD-related features from each rs-fMRI dataset, which can enhance the feature representation and interpretability of the model. The results show that our method outperforms state-of-the-art methods in terms of accuracy, sensitivity and specificity. This work provides a new perspective and solution for ASD identification based on rs-fMRI data using multi-task learning. It also demonstrates the potential and value of machine learning for advancing neuroscience research and clinical practice.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"27"},"PeriodicalIF":2.4,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11177385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316699","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":"Automated glioblastoma patient classification using hypoxia levels measured through magnetic resonance images.","authors":"Mohammad Amin Shahram, Hosein Azimian, Bita Abbasi, Zohreh Ganji, Zahra Khandan Khadem-Reza, Elham Khakshour, Hoda Zare","doi":"10.1186/s12868-024-00871-2","DOIUrl":"10.1186/s12868-024-00871-2","url":null,"abstract":"<p><strong>Introduction: </strong>The challenge of treating Glioblastoma (GBM) tumors is due to various mechanisms that make the tumor resistant to radiation therapy. One of these mechanisms is hypoxia, and therefore, determining the level of hypoxia can improve treatment planning and initial evaluation of its effectiveness in GBM. This study aimed to design an intelligent system to classify glioblastoma patients based on hypoxia levels obtained from magnetic resonance images with the help of an artificial neural network (ANN).</p><p><strong>Material and method: </strong>MR images and PET measurements were available for this study. MR images were downloaded from the Cancer Imaging Archive (TCIA) database to classify glioblastoma patients based on hypoxia. The images in this database were prepared from 27 patients with glioblastoma on T1W + Gd, T2W-FLAIR, and T2W. Our designed algorithm includes various parts of pre-processing, tumor segmentation, feature extraction from images, and matching these features with quantitative parameters related to hypoxia in PET images. The system's performance is evaluated by categorizing glioblastoma patients based on hypoxia.</p><p><strong>Results: </strong>The results of classification with the artificial neural network (ANN) algorithm were as follows: the highest sensitivity, specificity, and accuracy were obtained at 86.71, 85.99 and 83.17%, respectively. The best specificity was related to the T2W-EDEMA image with the tumor to blood ratio (TBR) as a hypoxia parameter. T1W-NECROSIS image with the TBR parameter also showed the highest sensitivity and accuracy.</p><p><strong>Conclusion: </strong>The results of the present study can be used in clinical procedures before treating glioblastoma patients. Among these treatment approaches, we can mention the radiotherapy treatment design and the prescription of effective drugs for the treatment of hypoxic tumors.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"26"},"PeriodicalIF":2.4,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092452","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":"Central nervous system anomalies in 41 Chinese children incontinentia pigmenti.","authors":"Li Yin, Zhengyuan Li, Wenjuan Zhan, Yuanjie Kang, Qian Tian, Dan Li, Huifang Zhang","doi":"10.1186/s12868-024-00872-1","DOIUrl":"10.1186/s12868-024-00872-1","url":null,"abstract":"<p><strong>Introduction: </strong>Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase.</p><p><strong>Materials and methods: </strong>This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi'an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data.</p><p><strong>Results: </strong>Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 10⁹), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 10⁹). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration.</p><p><strong>Conclusion: </strong>Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"25"},"PeriodicalIF":2.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075311","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":"Characterizing dysregulations via cell-cell communications in Alzheimer's brains using single-cell transcriptomes.","authors":"Che Yu Lee, Dylan Riffle, Yifeng Xiong, Nadia Momtaz, Yutong Lei, Joseph M Pariser, Diptanshu Sikdar, Ahyeon Hwang, Ziheng Duan, Jing Zhang","doi":"10.1186/s12868-024-00867-y","DOIUrl":"10.1186/s12868-024-00867-y","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic and genomic resolution by enabling scientists to explore the diversity of gene expression patterns at the finest resolution. Most existing studies have solely focused on molecular perturbations within each cell, but cells live in microenvironments rather than in isolated entities. Here, we leveraged the large-scale and publicly available single-nucleus RNA sequencing in the human prefrontal cortex to investigate cell-to-cell communication in healthy brains and their perturbations in AD. We uniformly processed the snRNA-seq with strict QCs and labeled canonical cell types consistent with the definitions from the BRAIN Initiative Cell Census Network. From ligand and receptor gene expression, we built a high-confidence cell-to-cell communication network to investigate signaling differences between AD and healthy brains.</p><p><strong>Results: </strong>Specifically, we first performed broad communication pattern analyses to highlight that biologically related cell types in normal brains rely on largely overlapping signaling networks and that the AD brain exhibits the irregular inter-mixing of cell types and signaling pathways. Secondly, we performed a more focused cell-type-centric analysis and found that excitatory neurons in AD have significantly increased their communications to inhibitory neurons, while inhibitory neurons and other non-neuronal cells globally decreased theirs to all cells. Then, we delved deeper with a signaling-centric view, showing that canonical signaling pathways CSF, TGFβ, and CX3C are significantly dysregulated in their signaling to the cell type microglia/PVM and from endothelial to neuronal cells for the WNT pathway. Finally, after extracting 23 known AD risk genes, our intracellular communication analysis revealed a strong connection of extracellular ligand genes APP, APOE, and PSEN1 to intracellular AD risk genes TREM2, ABCA1, and APP in the communication from astrocytes and microglia to neurons.</p><p><strong>Conclusions: </strong>In summary, with the novel advances in single-cell sequencing technologies, we show that cellular signaling is regulated in a cell-type-specific manner and that improper regulation of extracellular signaling genes is linked to intracellular risk genes, giving the mechanistic intra- and inter-cellular picture of AD.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"25 1","pages":"24"},"PeriodicalIF":2.4,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916220","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}