Pub Date : 2024-09-19DOI: 10.1016/j.neuroscience.2024.09.036
Chunyan Zhang , Feng Jiang , Shengqing Liu , Haibo Ni , Zhanchun Feng , Minye Huang , Yunwei Lu , Yinwei Qian , Jianfeng Shao , Qin Rui
The neuroinflammatory response promotes secondary brain injury after traumatic brain injury (TBI). Triggering receptor expressed on myeloid cells 1 (TREM1) is a key regulator of inflammation. However, the role of TREM1 in TBI is poorly studied. The purpose of this study was to investigate the role of TREM1 in TBI and the possible underlying mechanism. We found that the protein expression of TREM1 significantly increased after TBI in rats, and the TREM1 protein localized to microglia. Inhibition of the TREM1 protein with LP17 significantly blocked ERK phosphorylation and reduced cytoplasmic phospholipase A2 (cPLA2) protein expression and phosphorylation. In addition, LP17-mediated TREM1 inhibition significantly reduced the protein expression of iNOS and increased the protein expression of Arg1. Moreover, after TREM1 was inhibited, the secretion of the proinflammatory factors TNF-α and IL-1β was significantly reduced, while the secretion of the anti-inflammatory factors IL-4 and IL-10 was significantly increased. Additionally, inhibition of TREM1 by LP17 significantly reduced neuronal apoptosis and ameliorated nerve dysfunction in TBI model rats. In conclusion, our findings suggest that TREM1 enhances neuroinflammation and promotes neuronal apoptosis after TBI, and these effects may be partly mediated via the ERK/cPLA2 signalling pathway.
{"title":"TREM1 promotes neuroinflammation after traumatic brain injury in rats: Possible involvement of ERK/cPLA2 signalling pathway","authors":"Chunyan Zhang , Feng Jiang , Shengqing Liu , Haibo Ni , Zhanchun Feng , Minye Huang , Yunwei Lu , Yinwei Qian , Jianfeng Shao , Qin Rui","doi":"10.1016/j.neuroscience.2024.09.036","DOIUrl":"10.1016/j.neuroscience.2024.09.036","url":null,"abstract":"<div><div>The neuroinflammatory response promotes secondary brain injury after traumatic brain injury (TBI). Triggering receptor expressed on myeloid cells 1 (TREM1) is a key regulator of inflammation. However, the role of TREM1 in TBI is poorly studied. The purpose of this study was to investigate the role of TREM1 in TBI and the possible underlying mechanism. We found that the protein expression of TREM1 significantly increased after TBI in rats, and the TREM1 protein localized to microglia. Inhibition of the TREM1 protein with LP17 significantly blocked ERK phosphorylation and reduced cytoplasmic phospholipase A2 (cPLA2) protein expression and phosphorylation. In addition, LP17-mediated TREM1 inhibition significantly reduced the protein expression of iNOS and increased the protein expression of Arg1. Moreover, after TREM1 was inhibited, the secretion of the proinflammatory factors TNF-α and IL-1β was significantly reduced, while the secretion of the anti-inflammatory factors IL-4 and IL-10 was significantly increased. Additionally, inhibition of TREM1 by LP17 significantly reduced neuronal apoptosis and ameliorated nerve dysfunction in TBI model rats. In conclusion, our findings suggest that TREM1 enhances neuroinflammation and promotes neuronal apoptosis after TBI, and these effects may be partly mediated via the ERK/cPLA2 signalling pathway.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Binge eating disorder is the most prevalent eating disorder, affecting both sexes but more commonly found in women. Given the frequent co-occurrence of psychiatric disorders, this study aimed to establish a standardized experimental intermittent protocol to investigate overeating associated with depression. A 10-day protocol induced uncontrolled eating behavior in C57BL/6J female mice. The first experiment included the following groups: naive group (chow ad libitum), control group (chow and sucrose solution ad libitum), and fasting groups (16 and 20 h) exposed to an intermittent sucrose solution (10 %) and chow regimen. Subsequently, the feeding test, open field test, elevated plus maze test, tail suspension test, and light/dark conflict test were conducted. Furthermore, monoamine oxidase (MAO) A and B activities in brain structures and plasma corticosterone levels were assessed. Food overconsumption and depressive-like behavior were observed in both sucrose fasting groups, while risk-taking behaviors were specifically observed in the 20-hour fasting sucrose group. While both fasting sucrose groups caused reduced hippocampal MAO-A activity, only the F20 sucrose group inhibited MAO-B in the cortex and hypothalamus. Moreover, both fasting sucrose groups exhibited elevated corticosterone levels. In a separate design (Experiment 2), groups with 16 and 20 h of fasting alone (without sucrose) did not show the same behavioral results as the intermittent fasting sucrose groups, thus avoiding fasting bias. Based on these results, the 20-hour sucrose fasting group was chosen as the ideal protocol for mimicking overeating behavior associated with depression to investigate future therapeutic approaches for this comorbidity.
{"title":"Intermittent access to sugary drinks associated with fasting induces overeating and depressive-like behavior in female C57BL/6J mice","authors":"Mariana Parron Paim, Dianer Nornberg Strelow, Letícia Devantier Krüger, Larissa Sander Magalhães, Tácia Katiane Hall, César Augusto Brüning, Cristiani Folharini Bortolatto","doi":"10.1016/j.neuroscience.2024.09.028","DOIUrl":"10.1016/j.neuroscience.2024.09.028","url":null,"abstract":"<div><div>Binge eating disorder is the most prevalent eating disorder, affecting both sexes but more commonly found in women. Given the frequent co-occurrence of psychiatric disorders, this study aimed to establish a standardized experimental intermittent protocol to investigate overeating associated with depression. A 10-day protocol induced uncontrolled eating behavior in C57BL/6J female mice. The first experiment included the following groups: naive group (chow ad libitum), control group (chow and sucrose solution ad libitum), and fasting groups (16 and 20 h) exposed to an intermittent sucrose solution (10 %) and chow regimen. Subsequently, the feeding test, open field test, elevated plus maze test, tail suspension test, and light/dark conflict test were conducted. Furthermore, monoamine oxidase (MAO) A and B activities in brain structures and plasma corticosterone levels were assessed. Food overconsumption and depressive-like behavior were observed in both sucrose fasting groups, while risk-taking behaviors were specifically observed in the 20-hour fasting sucrose group. While both fasting sucrose groups caused reduced hippocampal MAO-A activity, only the F20 sucrose group inhibited MAO-B in the cortex and hypothalamus. Moreover, both fasting sucrose groups exhibited elevated corticosterone levels. In a separate design (Experiment 2), groups with 16 and 20 h of fasting alone (without sucrose) did not show the same behavioral results as the intermittent fasting sucrose groups, thus avoiding fasting bias. Based on these results, the 20-hour sucrose fasting group was chosen as the ideal protocol for mimicking overeating behavior associated with depression to investigate future therapeutic approaches for this comorbidity.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.neuroscience.2024.09.030
Thiago Amorim de Souza Lima, Martina Raissa Ribeiro, Malcon Carneiro de Brito, Elisa Mitiko Kawamoto
Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic β-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors.
{"title":"Impaired exploration induced by type 1 diabetes is related to locomotor activity rather than a reduction in motivation","authors":"Thiago Amorim de Souza Lima, Martina Raissa Ribeiro, Malcon Carneiro de Brito, Elisa Mitiko Kawamoto","doi":"10.1016/j.neuroscience.2024.09.030","DOIUrl":"10.1016/j.neuroscience.2024.09.030","url":null,"abstract":"<div><p>Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic β-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors.</p></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.neuroscience.2024.09.027
Zhi-Yuan Wei , Li-Ping Wang , Di Gao , Lin Zhu , Jun-Fan Wu , Jia Shi , Yu-Ning Li , Xiao-Dan Tang , Yan-Meng Feng , Xu-Bin Pan , Yun-Yun Jin , Yan-Shan Liu , Jian-Huan Chen
Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In this study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissue and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and to evaluate its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and repopulation were primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Furthermore, the expression of complement-related genes, such as C4b and Cd47, was substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis and provides new insights into its potential role in SAE.
{"title":"Bulk and single-cell RNA-seq analyses reveal canonical RNA editing associated with microglial homeostasis and its role in sepsis-associated encephalopathy","authors":"Zhi-Yuan Wei , Li-Ping Wang , Di Gao , Lin Zhu , Jun-Fan Wu , Jia Shi , Yu-Ning Li , Xiao-Dan Tang , Yan-Meng Feng , Xu-Bin Pan , Yun-Yun Jin , Yan-Shan Liu , Jian-Huan Chen","doi":"10.1016/j.neuroscience.2024.09.027","DOIUrl":"10.1016/j.neuroscience.2024.09.027","url":null,"abstract":"<div><div>Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In this study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissue and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and to evaluate its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of <em>Apobec1</em> and <em>Apobec3</em> at Day 5 and dramatically changed <em>B2m</em> RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and repopulation were primarily observed in synaptic genes, such as <em>Tbc1d24</em> and <em>Slc1a2.</em> ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of <em>Apobec1</em> and <em>Apobec3</em>, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated <em>Apobec1</em> and <em>Apobec3</em> expression, and altered RNA editing in immune-related genes, such as <em>B2m</em> and <em>Mier1</em>, and nervous-related lncRNA <em>Meg3</em> and <em>Snhg11</em>, both of which were repressed by microglial depletion. Furthermore, the expression of complement-related genes, such as <em>C4b</em> and <em>Cd47,</em> was substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis and provides new insights into its potential role in SAE.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.neuroscience.2024.09.025
Ying Wu , Zhi Zheng , Xue Bai , Ping Liu , Shanshan Hu , Lingxue Wang , Sijing Yang
Backgrounds
The role of miR-191-5p in cerebral ischemia–reperfusion (I/R) injury has been established, with its expression in endothelial cells demonstrating anti-angiogenic effects. A potential circular RNA, circRNA_0003307, has been identified through bioinformatics analysis as a candidate for interaction with miR-191-5p, yet its functional significance in brain I/R injury remains unexplored. We aimed to investigate whether circRNA_0003307 regulates brain microvascular endothelial cell (BMEC) vascular tube formation, invasion, and migration by regulating the miR-191-5p cascade.
Methods
Mouse BMECs (bEnd.3) were cultured and exposed to oxygen-glucose deprivation (OGD). The effects of circRNA_0003307 on vessel-like tube formation and cellular migration were examined. In addition, we investigated the protective effects of circRNA_0003307 on I/R injury in mice.
Results
The results showed the level of circRNA_0003307 was concentration-dependently increased in OGD-induced bEnd.3 cells. ODG-induction enhanced angiogenesis, migration, and invasion of bEnd.3 cells, which were further promoted by the transfection of pcDNA-0003307. Silencing circRNA_0003307 expression showed the opposite results. The dual luciferase assay demonstrated miRNA-191-5p interacted with circRNA_00033073′ UTR, and miRNA-191-5p could bind with CDK6. Meanwhile, circRNA_0003307 promoted the expression of CDK6 by sponging miRNA-191-5p. The overexpression of circRNA_0003307 activated the angiogenesis, migration, and invasion of OGD-induced bEnd.3 cells, which were hindered by miRNA-191-5p mimic or siRNA-CDK6. Thus, circRNA_0003307 promoted ODG-induced angiogenesis, migration, and invasion of bEnd.3 cells by targeting miR-191-5p/CDK6 axis. In vivo, circRNA_0003307 had protective effects on brain I/R injury, including neuroprotection, anti-apoptosis and angiogenesis.
Conclusion
CircRNA_0003307 may be a promising therapeutic target for the treatment of cerebral I/R injury.
{"title":"CircRNA_0003307 promoted brain microvascular endothelial cell angiogenesis, invasion, and migration in cerebral ischemia-reperfusion injury: Potential involvement of miRNA-191-5p/CDK6 pathway","authors":"Ying Wu , Zhi Zheng , Xue Bai , Ping Liu , Shanshan Hu , Lingxue Wang , Sijing Yang","doi":"10.1016/j.neuroscience.2024.09.025","DOIUrl":"10.1016/j.neuroscience.2024.09.025","url":null,"abstract":"<div><h3>Backgrounds</h3><div>The role of miR-191-5p in cerebral ischemia–reperfusion (I/R) injury has been established, with its expression in endothelial cells demonstrating anti-angiogenic effects. A potential circular RNA, circRNA_0003307, has been identified through bioinformatics analysis as a candidate for interaction with miR-191-5p, yet its functional significance in brain I/R injury remains unexplored. We aimed to investigate whether circRNA_0003307 regulates brain microvascular endothelial cell (BMEC) vascular tube formation, invasion, and migration by regulating the miR-191-5p cascade.</div></div><div><h3>Methods</h3><div>Mouse BMECs (bEnd.3) were cultured<!--> <!-->and exposed to oxygen-glucose deprivation (OGD). The effects of circRNA_0003307 on vessel-like tube formation and cellular migration were examined. In addition, we investigated the protective effects of circRNA_0003307 on I/R injury in mice.</div></div><div><h3>Results</h3><div>The results showed the level of circRNA_0003307 was concentration-dependently increased in OGD-induced bEnd.3 cells. ODG-induction enhanced angiogenesis, migration, and invasion of bEnd.3 cells, which were further promoted by the transfection of pcDNA-0003307. Silencing circRNA_0003307 expression showed the opposite results. The dual luciferase assay demonstrated miRNA-191-5p interacted with circRNA_00033073′ UTR, and miRNA-191-5p could bind with CDK6. Meanwhile, circRNA_0003307 promoted the expression of CDK6 by sponging miRNA-191-5p. The overexpression of circRNA_0003307 activated the angiogenesis, migration, and invasion of OGD-induced bEnd.3 cells, which were hindered by miRNA-191-5p mimic or siRNA-CDK6. Thus, circRNA_0003307 promoted ODG-induced angiogenesis, migration, and invasion of bEnd.3 cells by targeting miR-191-5p/CDK6 axis. In vivo, circRNA_0003307 had protective effects on brain I/R injury, including neuroprotection, anti-apoptosis and angiogenesis.</div></div><div><h3>Conclusion</h3><div>CircRNA_0003307 may be a promising<!--> <!-->therapeutic<!--> <!-->target for<!--> <!-->the treatment of cerebral I/R injury.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.neuroscience.2024.09.023
Yujin Jung, Sung-Hong Park
The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. For instance, the SAS around the middle cerebral artery is known to be highly involved in glymphatic influx. While diffusion tensor imaging has been used for studying the glymphatic system, there has been limited exploration of age-related changes in diffusion anisotropy within SAS and their regional variations. Given the narrow and heterogeneous morphology of SAS, the fractional anisotropy (FA) in diverse brain regions may be more relevant to glymphatic transport than mean diffusivity (MD). The goal of this study was to investigate FA in SAS to observe age-related changes across different brain regions and to interpret the results based on the glymphatic transport. We segmented SAS in the whole brain of 83 young adults and divided SAS into four cortical lobes. We demonstrated regional variations in FA and MD within SAS and an age-related decline in FA among young adults, indicating that diffusion within SAS becomes more isotropic with aging. These findings raise new questions about the factors influencing diffusion anisotropy within SAS, which are relevant to glymphatic transport.
glymphatic系统理论认为，脑废物是通过脑脊液（CSF）流清除的。根据这一理论，蛛网膜下腔（SAS）中的 CSF 移动到穿刺动脉周围的血管周围空间，流入实质内与间质和脑废物混合，然后移动到血管周围空间冲出大脑。尽管对glymphatic理论存在争议，但很明显，SAS在废物清除中起着关键作用。例如，已知大脑中动脉周围的 SAS 高度参与甘油流入。虽然弥散张量成像已被用于研究甘液系统，但对 SAS 内弥散各向异性与年龄相关的变化及其区域变化的探索还很有限。鉴于 SAS 的形态狭窄且不均匀，不同脑区的分数各向异性（FA）可能比平均扩散率（MD）与甘油运输更相关。本研究的目的是调查 SAS 的分数各向异性，以观察不同脑区与年龄相关的变化，并根据甘液运输对结果进行解释。我们对 83 名年轻成人的全脑进行了 SAS 分割，并将 SAS 划分为四个皮质叶。我们发现了SAS内FA和MD的区域差异，以及年轻成人FA与年龄相关的下降，这表明随着年龄的增长，SAS内的扩散变得更具各向同性。这些发现提出了新的问题，即影响 SAS 内扩散各向异性的因素，这些因素与甘液运输有关。
{"title":"Age-related brain-region-specific changes in diffusion anisotropy in subarachnoid space of young adults","authors":"Yujin Jung, Sung-Hong Park","doi":"10.1016/j.neuroscience.2024.09.023","DOIUrl":"10.1016/j.neuroscience.2024.09.023","url":null,"abstract":"<div><div>The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. For instance, the SAS around the middle cerebral artery is known to be highly involved in glymphatic influx. While diffusion tensor imaging has been used for studying the glymphatic system, there has been limited exploration of age-related changes in diffusion anisotropy within SAS and their regional variations. Given the narrow and heterogeneous morphology of SAS, the fractional anisotropy (FA) in diverse brain regions may be more relevant to glymphatic transport than mean diffusivity (MD). The goal of this study was to investigate FA in SAS to observe age-related changes across different brain regions and to interpret the results based on the glymphatic transport. We segmented SAS in the whole brain of 83 young adults and divided SAS into four cortical lobes. We demonstrated regional variations in FA and MD within SAS and an age-related decline in FA among young adults, indicating that diffusion within SAS becomes more isotropic with aging. These findings raise new questions about the factors influencing diffusion anisotropy within SAS, which are relevant to glymphatic transport.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.neuroscience.2024.09.011
J. Kokash , J.A. Rumschlag , K.A. Razak
Noise-induced hearing loss (NIHL) studies have focused on the lemniscal auditory pathway, but little is known about how NIHL impacts different cortical regions. Here we compared response recovery trajectories in the auditory and frontal cortices (AC, FC) of mice following NIHL. We recorded EEG responses from awake mice (male n = 15, female n = 14) before and following NIHL (longitudinal design) to quantify event related potentials and gap-in-noise temporal processing. Hearing loss was verified by measuring the auditory brainstem response (ABR) before and at 1-, 10-, 23–, and 45-days after noise-exposure. Resting EEG, event related potentials (ERP) and auditory steady state responses (ASSR) were recorded at the same time-points after NIHL. The inter-trial phase coherence (ITPC) of the ASSR was measured to quantify the ability of AC and FC to synchronize responses to short gaps embedded in noise. Despite the absence of click-evoked ABRs up to 90 dB SPL and up to 45-days post-exposure, ERPs from the AC and FC showed full recovery in ∼ 50 % of the mice to pre-NIHL levels in both AC and FC. The ASSR ITPC was reduced following NIHL in AC and FC in all the mice on day 1 after NIHL. The AC showed full recovery of ITPC over 45-days. Despite ERP amplitude recovery, the FC does not show recovery of ASSR ITPC. These results indicate post-NIHL plasticity with similar response amplitude recovery across AC and FC, but cortical region-specific trajectories in temporal processing recovery.
噪声诱发听力损失（NIHL）的研究主要集中在听觉通路，但对 NIHL 如何影响不同的皮层区域却知之甚少。在这里，我们比较了 NIHL 后小鼠听觉皮层和额叶皮层（AC、FC）的反应恢复轨迹。我们记录了清醒小鼠（雄性 n = 15，雌性 n = 14）在 NIHL 之前和之后的脑电图反应（纵向设计），以量化事件相关电位和噪声间隙时间处理。在暴露于噪声之前和之后的 1 天、10 天、23 天和 45 天，通过测量听性脑干反应（ABR）来验证听力损失。在 NIHL 后的相同时间点记录了静息脑电图、事件相关电位 (ERP) 和听觉稳态反应 (ASSR)。测量听觉稳态反应（ASSR）的试验间相位一致性（ITPC），以量化AC和FC对嵌入噪声的短间隙同步反应的能力。尽管在 90 dB SPL 和暴露后 45 天内没有点击诱发 ABRs，但 50% 的小鼠 AC 和 FC 的 ERPs 完全恢复到了 NIHL 前的水平。在 NIHL 后的第 1 天，所有小鼠的 AC 和 FC 在 NIHL 后的 ASSR ITPC 都降低了。AC 的 ITPC 在 45 天内完全恢复。尽管ERP振幅恢复了，但FC的ASSR ITPC并没有恢复。这些结果表明，NIHL 后的可塑性在 AC 和 FC 中具有相似的反应振幅恢复，但在时间处理恢复方面具有皮层区域特异性轨迹。
{"title":"Cortical region-specific recovery of auditory temporal processing following noise-induced hearing loss","authors":"J. Kokash , J.A. Rumschlag , K.A. Razak","doi":"10.1016/j.neuroscience.2024.09.011","DOIUrl":"10.1016/j.neuroscience.2024.09.011","url":null,"abstract":"<div><div>Noise-induced hearing loss (NIHL) studies have focused on the lemniscal auditory pathway, but little is known about how NIHL impacts different cortical regions. Here we compared response recovery trajectories in the auditory and frontal cortices (AC, FC) of mice following NIHL. We recorded EEG responses from awake mice (male n = 15, female n = 14) before and following NIHL (longitudinal design) to quantify event related potentials and gap-in-noise temporal processing. Hearing loss was verified by measuring the auditory brainstem response (ABR) before and at 1-, 10-, 23–, and 45-days after noise-exposure. Resting EEG, event related potentials (ERP) and auditory steady state responses (ASSR) were recorded at the same time-points after NIHL. The inter-trial phase coherence (ITPC) of the ASSR was measured to quantify the ability of AC and FC to synchronize responses to short gaps embedded in noise. Despite the absence of click-evoked ABRs up to 90 dB SPL and up to 45-days post-exposure, ERPs from the AC and FC showed full recovery in ∼ 50 % of the mice to pre-NIHL levels in both AC and FC. The ASSR ITPC was reduced following NIHL in AC and FC in all the mice on day 1 after NIHL. The AC showed full recovery of ITPC over 45-days. Despite ERP amplitude recovery, the FC does not show recovery of ASSR ITPC. These results indicate post-NIHL plasticity with similar response amplitude recovery across AC and FC, but cortical region-specific trajectories in temporal processing recovery.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.neuroscience.2024.09.029
Zhang Ling , Tian Qing , Xie Chunming
Suicide ideation (SI) is the major cause of death in persons with depression, whereas effective and accurate biomarkers for suicidal behavior of persons with depression are still lack. Recently, manifold studies in vivo revealed that epigenetic alterations including DNA methylation, non-coding RNA regulation, RNA editing and histone modification, were associated with depressive severity and SI, and peripheral epigenetic molecules may be potential biomarkers for suicidal risk of persons with depression. Therefore, we firstly reviewed recent epigenetic advancements in depression with suicide ideation (DSI) according to studies based on human tissue. Furthermore, we discussed the significance and potential of minimally-invasive peripheral epigenetic molecules to identify potential suicidal biomarkers for DSI, aiming to promote early identification and therapeutic evaluation of DSI.
{"title":"Epigenetic insight into the suicidal biomarker of depression with suicide Ideation: A narrative review","authors":"Zhang Ling , Tian Qing , Xie Chunming","doi":"10.1016/j.neuroscience.2024.09.029","DOIUrl":"10.1016/j.neuroscience.2024.09.029","url":null,"abstract":"<div><div>Suicide ideation (SI) is the major cause of death in persons with depression, whereas effective and accurate biomarkers for suicidal behavior of persons with depression are still lack. Recently, manifold studies <em>in vivo</em> revealed that epigenetic alterations including DNA methylation, non-coding RNA regulation, RNA editing and histone modification, were associated with depressive severity and SI, and peripheral epigenetic molecules may be potential biomarkers for suicidal risk of persons with depression. Therefore, we firstly reviewed recent epigenetic advancements in depression with suicide ideation (DSI) according to studies based on human tissue. Furthermore, we discussed the significance and potential of minimally-invasive peripheral epigenetic molecules to identify potential suicidal biomarkers for DSI, aiming to promote early identification and therapeutic evaluation of DSI.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.neuroscience.2024.09.012
Iara D. de Souza , Vítor G. S. Fernandes , João Vitor F. Cavalcante , Ana Carolina M. F. Coelho , Diego A. A. Morais , Otavio Cabral-Marques , Matheus A. B. Pasquali , Rodrigo J. S. Dalmolin
Major depressive disorder (MDD) is a leading global cause of disability, being more prevalent in females, possibly due to molecular and neuronal pathway differences between females and males. However, the connection between transcriptional changes and MDD remains unclear. We identified transcriptionally altered genes (TAGs) in MDD through gene and transcript expression analyses, focusing on sex-specific differences. Analyzing 263 brain samples from both sexes, we conducted differential gene expression, differential transcript expression, and differential transcript usage analyses, revealing 1169 unique TAGs, primarily in the prefrontal areas, with nearly half exhibiting transcript-level alterations. Females showed notable RNA splicing and export process disruptions in the orbitofrontal cortex, alongside altered DDX39B gene expression in five of the six brain regions in both sexes. Our findings suggest that disruptions in RNA processing pathways may play a vital role in MDD.
{"title":"Sex-specific gene expression differences in the prefrontal cortex of major depressive disorder individuals","authors":"Iara D. de Souza , Vítor G. S. Fernandes , João Vitor F. Cavalcante , Ana Carolina M. F. Coelho , Diego A. A. Morais , Otavio Cabral-Marques , Matheus A. B. Pasquali , Rodrigo J. S. Dalmolin","doi":"10.1016/j.neuroscience.2024.09.012","DOIUrl":"10.1016/j.neuroscience.2024.09.012","url":null,"abstract":"<div><p>Major depressive disorder (MDD) is a leading global cause of disability, being more prevalent in females, possibly due to molecular and neuronal pathway differences between females and males. However, the connection between transcriptional changes and MDD remains unclear. We identified transcriptionally altered genes (TAGs) in MDD through gene and transcript expression analyses, focusing on sex-specific differences. Analyzing 263 brain samples from both sexes, we conducted differential gene expression, differential transcript expression, and differential transcript usage analyses, revealing 1169 unique TAGs, primarily in the prefrontal areas, with nearly half exhibiting transcript-level alterations. Females showed notable RNA splicing and export process disruptions in the orbitofrontal cortex, alongside altered DDX39B gene expression in five of the six brain regions in both sexes. Our findings suggest that disruptions in RNA processing pathways may play a vital role in MDD.</p></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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