Brain, Behavior, and Immunity最新文献_第7页

Analysis of the brain transcriptome, microbiome and metabolome in ketogenic diet and experimental stroke 生酮饮食与实验性中风的脑转录组、微生物组和代谢组分析。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-10-06 DOI: 10.1016/j.bbi.2024.10.004

Anastasia A. Zharikova , Nadezda V. Andrianova , Denis N. Silachev , Vladimir O. Nebogatikov , Irina B. Pevzner , Ciara I. Makievskaya , Ljubava D. Zorova , Grigoriy V. Maleev , Galina V. Baydakova , Dmitry V. Chistyakov , Sergey V. Goriainov , Marina G. Sergeeva , Inna Y. Burakova , Artem P. Gureev , Vasily A. Popkov , Aleksey A. Ustyugov , Egor Y. Plotnikov

{"title":"Analysis of the brain transcriptome, microbiome and metabolome in ketogenic diet and experimental stroke","authors":"Anastasia A. Zharikova , Nadezda V. Andrianova , Denis N. Silachev , Vladimir O. Nebogatikov , Irina B. Pevzner , Ciara I. Makievskaya , Ljubava D. Zorova , Grigoriy V. Maleev , Galina V. Baydakova , Dmitry V. Chistyakov , Sergey V. Goriainov , Marina G. Sergeeva , Inna Y. Burakova , Artem P. Gureev , Vasily A. Popkov , Aleksey A. Ustyugov , Egor Y. Plotnikov","doi":"10.1016/j.bbi.2024.10.004","DOIUrl":"10.1016/j.bbi.2024.10.004","url":null,"abstract":"<div><div>The ketogenic diet (KD) has been shown to be effective in treating various brain pathologies. In this study, we conducted detailed transcriptomic and metabolomic profiling of rat brains after KD and ischemic stroke in order to investigate the effects of KD and its underlying mechanisms. We evaluated the effect of a two-month KD on gene expression in intact brain tissue and after middle cerebral artery occlusion (MCAO). We analyzed the effects of KD on gut microbiome composition and blood metabolic profile as well as investigated the correlation between severity of neurological deficits and KD-induced changes. We found transcriptional reprogramming in the brain after stroke and KD treatment. The KD altered the expression of genes involved in the regulation of glucose and fatty acid metabolism, mitochondrial function, the immune response, Wnt-associated signaling, stem cell development, and neurotransmission, both in intact rats and after MCAO. The KD led to a significant change in the composition of gut microbiome and the levels of amino acids, acylcarnitines, polyunsaturated fatty acids, and oxylipins in the blood. However, the KD slightly worsened the neurological functions after MCAO, so that the therapeutic effect of the diet remained unproven.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 571-585"},"PeriodicalIF":8.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frontiers of Neurodegenerative Disease Treatment: Targeting Immune Cells in Brain Border Regions 神经变性疾病治疗的前沿：瞄准大脑边界区域的免疫细胞。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-10-06 DOI: 10.1016/j.bbi.2024.10.007

Senthil Kumaran Satyanarayanan , Zixu Han , Jingwei Xiao , Qiuju Yuan , Wing Ho Yung , Ya Ke , Raymond Chuen-Chung Chang , Maria Huachen Zhu , Huanxing Su , Kuan-Pin Su , Dajiang Qin , Suki Man Yan Lee

{"title":"Frontiers of Neurodegenerative Disease Treatment: Targeting Immune Cells in Brain Border Regions","authors":"Senthil Kumaran Satyanarayanan , Zixu Han , Jingwei Xiao , Qiuju Yuan , Wing Ho Yung , Ya Ke , Raymond Chuen-Chung Chang , Maria Huachen Zhu , Huanxing Su , Kuan-Pin Su , Dajiang Qin , Suki Man Yan Lee","doi":"10.1016/j.bbi.2024.10.007","DOIUrl":"10.1016/j.bbi.2024.10.007","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDs) demonstrate a complex interaction with the immune system, challenging the traditional view of the brain as an “immune-privileged” organ. Microglia were once considered the sole guardians of the brain’s immune response. However, recent research has revealed the critical role of peripheral immune cells located in key brain regions like the meninges, choroid plexus, and perivascular spaces. These previously overlooked cells are now recognized as contributors to the development and progression of NDs. This newfound understanding opens doors for pioneering therapeutic strategies. By targeting these peripheral immune cells, we may be able to modulate the brain’s immune environment, offering an alternative approach to treat NDs and circumvent the challenges posed by the blood–brain barrier. This comprehensive review will scrutinize the latest findings on the complex interactions between these peripheral immune cells and NDs. It will also critically assess the prospects of targeting these cells as a ground-breaking therapeutic avenue for these debilitating disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 483-499"},"PeriodicalIF":8.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondria at the crossroad of dysregulated inflammatory and metabolic processes in bipolar disorders 线粒体是双相情感障碍中炎症和代谢过程失调的交叉点。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-10-06 DOI: 10.1016/j.bbi.2024.10.008

Jérémy Bernard , Ryad Tamouza , Ophélia Godin , Michael Berk , Ana C. Andreazza , Marion Leboyer

{"title":"Mitochondria at the crossroad of dysregulated inflammatory and metabolic processes in bipolar disorders","authors":"Jérémy Bernard , Ryad Tamouza , Ophélia Godin , Michael Berk , Ana C. Andreazza , Marion Leboyer","doi":"10.1016/j.bbi.2024.10.008","DOIUrl":"10.1016/j.bbi.2024.10.008","url":null,"abstract":"<div><div>In last few decades, considerable evidence has emphasized the significant involvement of mitochondria, often referred to as the “powerhouse of the cell,” in the pathophysiology of bipolar disorder (BD). Given crucial mitochondrial functions in cellular metabolism and inflammation, both of which are compromised in BD, this perspective review examines the central role of mitochondria in inflammation and metabolism within the context of this disorder. We first describe the significance of mitochondria in metabolism before presenting the dysregulated inflammatory and metabolic processes. Then, we present a synthetic and hypothetical model of the importance of mitochondria in those dysfunctional pathways. The article also reviews different techniques for assessing mitochondrial function and discuss diagnostic and therapeutic implications. This review aims to improve the understanding of the inflammatory and metabolic comorbidities associated with bipolar disorders along with mitochondrial alterations within this context.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 456-465"},"PeriodicalIF":8.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metagenomic symphony of the intestinal ecosystem: How the composition affects the mind 肠道生态系统的元基因组交响乐：构成如何影响心灵

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-10-04 DOI: 10.1016/j.bbi.2024.09.033

Stefanie Malan-Müller , David Martín-Hernández , Javier R. Caso , Jelle Matthijnssens , Amanda Rodríguez-Urrutia , Christopher A. Lowry , Juan C. Leza

{"title":"Metagenomic symphony of the intestinal ecosystem: How the composition affects the mind","authors":"Stefanie Malan-Müller , David Martín-Hernández , Javier R. Caso , Jelle Matthijnssens , Amanda Rodríguez-Urrutia , Christopher A. Lowry , Juan C. Leza","doi":"10.1016/j.bbi.2024.09.033","DOIUrl":"10.1016/j.bbi.2024.09.033","url":null,"abstract":"<div><div>Mental health disorders and neurodegenerative diseases place a heavy burden on patients and societies, and, although great strides have been made to understand the pathophysiology of these conditions, advancement in drug development is lagging. The importance of gastrointestinal health in maintaining overall health and preventing disease is not a new concept. Hundreds of years ago, healers from various cultures and civilizations recognized the crucial role of the gut in sustaining health. More than a century ago, scientists began exploring the restorative effects of probiotics, marking the early recognition of the importance of gut microbes. The omics era brought more enlightenment and enabled researchers to identify the complexity of the microbial ecosystems we harbour, encompassing bacteria, eukaryotes (including fungi), archaea, viruses, and other microorganisms. The extensive genetic capacity of the microbiota is dynamic and influenced by the environment. The microbiota therefore serves as a significant entity within us, with evolutionarily preserved functions in host metabolism, immunity, development, and behavior. The significant role of the bacterial gut microbiome in mental health and neurodegenerative disorders has been realized and described within the framework of the microbiota-gut-brain axis. However, the bacterial members do not function unaccompanied, but rather in concert, and there is a substantial knowledge gap regarding the involvement of non-bacterial microbiome members in these disorders. In this review, we will explore the current literature that implicates a role for the entire metagenomic ensemble, and how their complex interkingdom relationships could influence CNS functioning in mental health disorders and neurodegenerative diseases.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathways to maternal health inequities: Structural racism, sleep, and physiological stress 孕产妇健康不平等的途径：结构性种族主义、睡眠和生理压力。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-10-02 DOI: 10.1016/j.bbi.2024.09.037

Lisa M. Christian , Ryan L. Brown , Judith E. Carroll , Julian F. Thayer , Tené T. Lewis , Shannon L. Gillespie , Christopher P. Fagundes

{"title":"Pathways to maternal health inequities: Structural racism, sleep, and physiological stress","authors":"Lisa M. Christian , Ryan L. Brown , Judith E. Carroll , Julian F. Thayer , Tené T. Lewis , Shannon L. Gillespie , Christopher P. Fagundes","doi":"10.1016/j.bbi.2024.09.037","DOIUrl":"10.1016/j.bbi.2024.09.037","url":null,"abstract":"<div><div>Racial inequities in health are vast and well-documented, particularly regarding maternal and infant health. Sleep health, including but not limited to duration and quality, is central to overall health and well-being. However, research has not adequately addressed how racism embedded in structures and systems, in addition to individual experiences, may affect maternal health by impacting sleep. In this critical review, we aim to 1) synthesize findings, emphasizing collaborative studies within our group, 2) highlight gaps in knowledge, and 3) propose a theoretical framework and methodological approach for moving the field forward. Specifically, we focus on findings and future directions linking perinatal sleep, cardiovascular and immune function, and racial disparities in maternal health. Because too few studies look beyond individual-level determinants of sleep deficiencies among Black Americans, we assert a critical need for research that bridges multiple levels of analysis (e.g., individual, community, society) and provides recommendations for specific health parameters that researchers in this area can target. Although the need to understand and address perinatal health disparities is clear, the goal of identifying multilevel mechanisms underlying how racism in one’s environment and daily life may interact to affect health extends far beyond pregnancy research.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Communication of inflammation 炎症的传播。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-09-30 DOI: 10.1016/j.bbi.2024.09.036

Michael B. Hennessy

引用次数: 0

Microglial TREM2 promotes phagocytic clearance of damaged neurons after status epilepticus 小胶质细胞 TREM2 促进对癫痫状态后受损神经元的吞噬清除。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-09-29 DOI: 10.1016/j.bbi.2024.09.034

Dale B. Bosco , Vaclav Kremen , Koichiro Haruwaka , Shunyi Zhao , Lingxiao Wang , Blake A. Ebner , Jiaying Zheng , Manling Xie , Aastha Dheer , Jadyn F. Perry , Abhijeet Barath , Aivi T. Nguyen , Gregory A. Worrell , Long-Jun Wu

{"title":"Microglial TREM2 promotes phagocytic clearance of damaged neurons after status epilepticus","authors":"Dale B. Bosco , Vaclav Kremen , Koichiro Haruwaka , Shunyi Zhao , Lingxiao Wang , Blake A. Ebner , Jiaying Zheng , Manling Xie , Aastha Dheer , Jadyn F. Perry , Abhijeet Barath , Aivi T. Nguyen , Gregory A. Worrell , Long-Jun Wu","doi":"10.1016/j.bbi.2024.09.034","DOIUrl":"10.1016/j.bbi.2024.09.034","url":null,"abstract":"<div><div>In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer’s disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute <em>status epilepticus</em> and the number of spontaneous recurrent seizures characteristic of chronic focal epilepsy. Phagocytic clearance of damaged neurons by microglia was also impaired by TREM2 KO and reduced phagocytic activity correlated with increased spontaneous seizures. Analysis of human tissue from patients who underwent surgical resection for drug resistant temporal lobe epilepsy also showed a negative correlation between expression of the microglial phagocytic marker CD68 and focal to bilateral tonic-clonic generalized seizure history. These results indicate that microglial TREM2 and phagocytic activity are important to epileptogenic pathology.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 540-555"},"PeriodicalIF":8.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain 脑膜白细胞介素-10上调δ类阿片受体可预防复发性疼痛

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-09-29 DOI: 10.1016/j.bbi.2024.09.031

Kufreobong E. Inyang , Jaewon Sim , Kimberly B. Clark , Matan Geron , Karli Monahan , Christine Evans , Patrick O’Connell , Sophie Laumet , Bo Peng , Jiacheng Ma , Cobi J. Heijnen , Robert Dantzer , Grégory Scherrer , Annemieke Kavelaars , Matthew Bernard , Yasser A. Aldhamen , Joseph K. Folger , Alexis Bavencoffe , Geoffroy Laumet

{"title":"Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain","authors":"Kufreobong E. Inyang , Jaewon Sim , Kimberly B. Clark , Matan Geron , Karli Monahan , Christine Evans , Patrick O’Connell , Sophie Laumet , Bo Peng , Jiacheng Ma , Cobi J. Heijnen , Robert Dantzer , Grégory Scherrer , Annemieke Kavelaars , Matthew Bernard , Yasser A. Aldhamen , Joseph K. Folger , Alexis Bavencoffe , Geoffroy Laumet","doi":"10.1016/j.bbi.2024.09.031","DOIUrl":"10.1016/j.bbi.2024.09.031","url":null,"abstract":"<div><div>Chronic pain often includes periods of transient amelioration and even remission that alternate with severe relapsing pain. While most research on chronic pain has focused on pain development and maintenance, there is a critical unmet need to better understand the mechanisms that underlie pain remission and relapse. We found that interleukin (IL)-10, a pain resolving cytokine, is produced by resident macrophages in the spinal meninges during remission from pain and signaled to IL-10 receptor-expressing sensory neurons. Using unbiased RNA-sequencing, we identified that IL-10 upregulated expression and antinociceptive activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of either IL-10 signaling or δOR triggered relapsing pain. Overall, our findings, from electrophysiology, genetic manipulation, flow cytometry, pharmacology, and behavioral approaches, indicate that remission of pain is not simply a return to the naïve state. Instead, remission is an adapted homeostatic state associated with lasting pain vulnerability resulting from persisting neuroimmune interactions within the nociceptive system. Broadly, this sheds light on the elusive mechanisms underlying recurrence a common aspect across various chronic pain conditions.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 399-410"},"PeriodicalIF":8.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammatory pain resolution by mouse serum-derived small extracellular vesicles 小鼠血清源性小细胞外囊泡缓解炎性疼痛。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-09-29 DOI: 10.1016/j.bbi.2024.09.032

Zhucheng Lin , Xuan Luo , Jason R. Wickman , Deepa Reddy , Jason T. DaCunza , Richa Pande , Yuzhen Tian , Ezgi E. Kasimoglu , Vivian Triana , Jingyun Lee , Cristina M. Furdui , Desmond Pink , Ahmet Sacan , Seena K. Ajit

{"title":"Inflammatory pain resolution by mouse serum-derived small extracellular vesicles","authors":"Zhucheng Lin , Xuan Luo , Jason R. Wickman , Deepa Reddy , Jason T. DaCunza , Richa Pande , Yuzhen Tian , Ezgi E. Kasimoglu , Vivian Triana , Jingyun Lee , Cristina M. Furdui , Desmond Pink , Ahmet Sacan , Seena K. Ajit","doi":"10.1016/j.bbi.2024.09.032","DOIUrl":"10.1016/j.bbi.2024.09.032","url":null,"abstract":"<div><div>Current treatments for chronic pain have limited efficacy and significant side effects, warranting research on alternative strategies for pain management. One approach involves using small extracellular vesicles (sEVs), or exosomes, to transport beneficial biomolecular cargo to aid pain resolution. Exosomes are 30–150 nm sEVs that can be beneficial or harmful depending on their source and cargo composition. We report a comprehensive multi-modal analysis of different aspects of sEV characterization, miRNAs, and protein markers across sEV sources. To investigate the short- and long-term effects of mouse serum-derived sEVs in pain modulation, sEVs from naïve control or spared nerve injury (SNI) model male donor mice were injected intrathecally into naïve male recipient mice. These sEVs transiently increased basal mechanical thresholds, an effect mediated by opioid signaling as this outcome was blocked by naltrexone. Mass spectrometry of sEVs detected endogenous opioid peptide leu-enkephalin. sEVs from naïve female mice have higher levels of leu-enkephalin compared to male, matching the analgesic onset of leu-enkephalin in male recipient mice. In investigating the long-term effect of sEVs, we observed that a single prophylactic intrathecal injection of sEVs two weeks prior to induction of the pain model in recipient mice accelerated recovery from inflammatory pain after complete Freund’s adjuvant (CFA) injection. Our exploratory studies examining immune cell populations in spinal cord and dorsal root ganglion using ChipCytometry suggested alterations in immune cell populations 14 days post-CFA. Flow cytometry confirmed increases in CD206<sup>+</sup> macrophages in the spinal cord in sEV-treated mice. Collectively, these studies demonstrate multiple mechanisms by which sEVs can attenuate pain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 422-441"},"PeriodicalIF":8.8,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sleep loss-induced oncogenic pathways are mediated via the neuron-specific interleukin-1 receptor accessory protein (AcPb) 睡眠不足诱导的致癌途径是通过神经元特异性白细胞介素-1受体附属蛋白（AcPb）介导的。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2024-09-28 DOI: 10.1016/j.bbi.2024.09.029

Yool Lee , Erika L. English , Catherine M. Schwartzmann , Yiyong Liu , James M. Krueger

{"title":"Sleep loss-induced oncogenic pathways are mediated via the neuron-specific interleukin-1 receptor accessory protein (AcPb)","authors":"Yool Lee , Erika L. English , Catherine M. Schwartzmann , Yiyong Liu , James M. Krueger","doi":"10.1016/j.bbi.2024.09.029","DOIUrl":"10.1016/j.bbi.2024.09.029","url":null,"abstract":"<div><div>Interleukin-1β (IL1), a pleiotropic cytokine, is involved in sleep regulation, tumor ontogeny, and immune responses. IL1 receptor adaptor proteins, including the IL1 receptor accessory protein (AcP), and its neuron-specific isoform, AcPb, are required for IL1 signaling. The AcPb isoform is resultant from alternate splicing of the AcP transcript. Our previous studies using AcPb null (AcPb<sup>-/-</sup>) mice characterized its participation in sleep regulation and emergent neuronal/glial network properties. Here, we investigated the impact of acute sleep disruption (SD) on brain cancer-related pathways in wild-type (WT) and AcPb<sup>-/-</sup> mice, employing RNA sequencing methods. In WT mice, SD increased AcPb mRNA levels, but not AcP mRNA, confirming prior similar work in rats. Transcriptome and pathway enrichment analyses demonstrated significant alterations in cancer, immune, and viral disease-related pathways in WT mice after SD, which were attenuated in AcPb<sup>-/-</sup> mice including multiple upregulated Src phosphorylation-signaling-dependent genes associated with cancer progression and metastasis. Our RNAseq findings, were analyzed within the context of The Cancer Genome Atlas Program (TCGA) data base; revealing an upregulation of sleep- and cancer-linked genes (e.g., IL-17B, IL-17RA, LCN2) across various tumors, including brain tumors, compared to normal tissues. Sleep-linked factors, identified through TCGA analyses, significantly impact patient prognosis and survival, particularly in low-grade glioma (LGG) and glioblastoma multiforme (GBM) patients. Overall, our findings suggest that SD promotes a pro-tumor environment through AcPb-modulated pathways.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 411-421"},"PeriodicalIF":8.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0