scholarly journals eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data

2018 ◽  
Author(s):  
Yann Le Guen ◽  
Cathy Philippe ◽  
Denis Riviere ◽  
Hervé Lemaitre ◽  
Antoine Grigis ◽  
...  
Keyword(s):  
Immune Cell ◽  
Magnetic Resonance Images ◽  
Cortical Atrophy ◽  
Uk Biobank ◽  
Cns Inflammation ◽  
Neuroimaging Data ◽  
The Central Nervous System ◽  
Trait Locus ◽  
The Uk ◽  
The Brain

AbstractThe grey and white matter volumes are known to reduce with age. This cortical shrinkage is visible on magnetic resonance images and is conveniently identified by the increased volume of cerebrospinal fluid in the sulci between two gyri. Here, we replicated this finding using the UK Biobank dataset and studied the genetic influence on these cortical features of aging. We divided all individuals genetically confirmed of British ancestry into two sub-cohorts (12,162 and 3,435 subjects for discovery and replication samples, respectively). We found that the heritability of the sulcal opening ranges from 15 to 45% (s.e.= 4.8%). We identified 4 new loci that contribute to this opening, including one that also affects the sulci grey matter thickness. We identified the most significant variant (rs864736) on this locus as being an expression quantitative trait locus (eQTL) for the KCNK2 gene. This gene regulates the immune-cell into the central nervous system (CNS) and controls the CNS inflammation, which is implicated in cortical atrophy and cognitive decline. These results expand our knowledge of the genetic contribution to cortical shrinking and promote further investigation into these variants and genes in pathological context such as Alzheimer’s disease in which brain shrinkage is a key biomarker.

scholarly journals Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations—A Short Overview

2021 ◽  
Vol 22 (11) ◽  
pp. 6141
Author(s):  
Teodora Larisa Timis ◽  
Ioan Alexandru Florian ◽  
Sergiu Susman ◽  
Ioan Stefan Florian
Keyword(s):  
Immune Cells ◽  
Arteriovenous Malformations ◽  
Intracranial Aneurysms ◽  
Immune Cell ◽  
Vascular Malformations ◽  
Cerebral Injury ◽  
Future Research ◽  
Mortality And Morbidity ◽  
The Central Nervous System ◽  
The Brain

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.

Medical relevance of common protein-altering variants in GPCR genes across 337,205 individuals in the UK Biobank

2019 ◽  
Author(s):  
Christopher DeBoever ◽  
AJ Venkatakrishnan ◽  
Joseph M Paggi ◽  
Franziska M. Heydenreich ◽  
Suli-Anne Laurin ◽  
...  
Keyword(s):  
Drug Targets ◽  
Immune Cell ◽  
Gastric Inhibitory Polypeptide ◽  
Uk Biobank ◽  
Genetic Associations ◽  
Downstream Signaling ◽  
Cell Counts ◽  
Future Drug ◽  
The Uk ◽  
Coding Variants

AbstractG protein-coupled receptors (GPCRs) drive an array of critical physiological functions and are an important class of drug targets, though a map of which GPCR genetic variants are associated with phenotypic variation is lacking. We performed a phenome-wide association analysis for 269 common protein-altering variants in 156 GPCRs and 275 phenotypes, including disease outcomes and diverse quantitative measurements, using 337,205 UK Biobank participants and identified 138 associations. We discovered novel associations between GPCR variants and migraine risk, hypothyroidism, and dietary consumption. We also demonstrated experimentally that variants in the β2 adrenergic receptor (ADRB2) associated with immune cell counts and pulmonary function and variants in the gastric inhibitory polypeptide receptor (GIPR) associated with food intake and body size affect downstream signaling pathways. Overall, this study provides a map of genetic associations for GPCR coding variants across a wide variety of phenotypes, which can inform future drug discovery efforts targeting GPCRs.

scholarly journals Large-scale analysis of iliopsoas muscle volumes in the UK Biobank

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julie A. Fitzpatrick ◽  
Nicolas Basty ◽  
Madeleine Cule ◽  
Yi Liu ◽  
Jimmy D. Bell ◽  
...  
Keyword(s):  
Large Scale ◽  
Large Population ◽  
Psoas Muscle ◽  
Magnetic Resonance Images ◽  
Muscle Volume ◽  
Iliopsoas Muscle ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Automated Method ◽  
The Uk

AbstractPsoas muscle measurements are frequently used as markers of sarcopenia and predictors of health. Manually measured cross-sectional areas are most commonly used, but there is a lack of consistency regarding the position of the measurement and manual annotations are not practical for large population studies. We have developed a fully automated method to measure iliopsoas muscle volume (comprised of the psoas and iliacus muscles) using a convolutional neural network. Magnetic resonance images were obtained from the UK Biobank for 5000 participants, balanced for age, gender and BMI. Ninety manual annotations were available for model training and validation. The model showed excellent performance against out-of-sample data (average dice score coefficient of 0.9046 ± 0.0058 for six-fold cross-validation). Iliopsoas muscle volumes were successfully measured in all 5000 participants. Iliopsoas volume was greater in male compared with female subjects. There was a small but significant asymmetry between left and right iliopsoas muscle volumes. We also found that iliopsoas volume was significantly related to height, BMI and age, and that there was an acceleration in muscle volume decrease in men with age. Our method provides a robust technique for measuring iliopsoas muscle volume that can be applied to large cohorts.

scholarly journals Regulated Release of Cryptococcal Polysaccharide Drives Virulence and Suppresses Immune Cell Infiltration into the Central Nervous System

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Steven T. Denham ◽  
Surbhi Verma ◽  
Raymond C. Reynolds ◽  
Colleen L. Worne ◽  
Joshua M. Daugherty ◽  
...  
Keyword(s):  
Cell Size ◽  
Immune Cell ◽  
Opportunistic Pathogen ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Content Type ◽  
The Central Nervous System ◽  
Capsule Thickness ◽  
The Brain

ABSTRACTCryptococcus neoformansis a common environmental yeast and opportunistic pathogen responsible for 15% of AIDS-related deaths worldwide. Mortality primarily results from meningoencephalitis, which occurs when fungal cells disseminate to the brain from the initial pulmonary infection site. A keyC. neoformansvirulence trait is the polysaccharide capsule. Capsule shieldsC. neoformansfrom immune-mediated recognition and destruction. The main capsule component, glucuronoxylomannan (GXM), is found both attached to the cell surface and free in the extracellular space (as exo-GXM). Exo-GXM accumulates in patient serum and cerebrospinal fluid at microgram/milliliter concentrations, has well-documented immunosuppressive properties, and correlates with poor patient outcomes. However, it is poorly understood whether exo-GXM release is regulated or the result of shedding during normal capsule turnover. We demonstrate that exo-GXM release is regulated by environmental cues and inversely correlates with surface capsule levels. We identified genes specifically involved in exo-GXM release that do not alter surface capsule thickness. The first mutant, theliv7Δ strain, released less GXM than wild-type cells when capsule was not induced. The second mutant, thecnag_00658Δ strain, released more exo-GXM under capsule-inducing conditions. Exo-GXM release observedin vitrocorrelated with polystyrene adherence, virulence, and fungal burden during murine infection. Additionally, we found that exo-GXM reduced cell size and capsule thickness under capsule-inducing conditions, potentially influencing dissemination. Finally, we demonstrated that exo-GXM prevents immune cell infiltration into the brain during disseminated infection and highly inflammatory intracranial infection. Our data suggest that exo-GXM performs a distinct role from capsule GXM during infection, altering cell size and suppressing inflammation.

scholarly journals Neuroinvasion of SARS-CoV-2 in human and mouse brain

2021 ◽  
Vol 218 (3) ◽  
Author(s):  
Eric Song ◽  
Ce Zhang ◽  
Benjamin Israelow ◽  
Alice Lu-Culligan ◽  
Alba Vieites Prado ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Immune Cell ◽  
Multiple Organ ◽  
Type I ◽  
Organ Systems ◽  
The Central Nervous System ◽  
Interferon Responses ◽  
The Brain ◽  
Immune Cell Infiltrates

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

scholarly journals Microglia: A Potential Therapeutic Target for Sepsis-Associated Encephalopathy and Sepsis-Associated Chronic Pain

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi Li ◽  
Lu Yin ◽  
Zhongmin Fan ◽  
Binxiao Su ◽  
Yu Chen ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Neurological Dysfunction ◽  
Potential Therapeutic Target ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
The Brain

Neurological dysfunction, one of the severe manifestations of sepsis in patients, is closely related to increased mortality and long-term complications in intensive care units, including sepsis-associated encephalopathy (SAE) and chronic pain. The underlying mechanisms of these sepsis-induced neurological dysfunctions are elusive. However, it has been well established that microglia, the dominant resident immune cell in the central nervous system, play essential roles in the initiation and development of SAE and chronic pain. Microglia can be activated by inflammatory mediators, adjacent cells and neurotransmitters in the acute phase of sepsis and then induce neuronal dysfunction in the brain. With the spotlight focused on the relationship between microglia and sepsis, a deeper understanding of microglia in SAE and chronic pain can be achieved. More importantly, clarifying the mechanisms of sepsis-associated signaling pathways in microglia would shed new light on treatment strategies for SAE and chronic pain.

scholarly journals eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data

2018 ◽  
Vol 224 (2) ◽  
pp. 847-857 ◽  
Author(s):  
Yann Le Guen ◽  
Cathy Philippe ◽  
Denis Riviere ◽  
Hervé Lemaitre ◽  
Antoine Grigis ◽  
...  
Keyword(s):  
Uk Biobank ◽  
Neuroimaging Data ◽  
The Brain

scholarly journals Physiology of Microglia

2011 ◽  
Vol 91 (2) ◽  
pp. 461-553 ◽  
Author(s):  
Helmut Kettenmann ◽  
Uwe-Karsten Hanisch ◽  
Mami Noda ◽  
Alexei Verkhratsky
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cell ◽  
Brain Parenchyma ◽  
Microglial Cells ◽  
Activation Process ◽  
Normal Brain ◽  
The Central Nervous System ◽  
Cellular Compartments ◽  
The Brain

Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Squash Cytology of a Dural-Based High-Grade Chondrosarcoma May Mimic That of Glioblastoma in the Central Nervous System

2015 ◽  
Vol 59 (2) ◽  
pp. 219-224 ◽  
Author(s):  
Sangho Lee ◽  
Na Rae Kim ◽  
Dong Hae Chung ◽  
Gi-Taek Yee ◽  
Hyun Yee Cho
Keyword(s):  
Magnetic Resonance Images ◽  
Temporal Area ◽  
Brain Invasion ◽  
S 100 ◽  
Radiation History ◽  
The Central Nervous System ◽  
Meningeal Tumors ◽  
Memory Disturbance ◽  
Well Differentiated ◽  
The Brain

Background: Intracranial chondrosarcoma is rare, and most cases occur in the skull base. Intradural chondrosarcoma is even rarer. Case: Here, we describe a case of dural chondrosarcoma with a radiation history for nasopharyngeal carcinoma and a radical prostatectomy for prostatic cancer 15 and 8 years earlier, respectively. A 67-year-old man presented with a 3-week memory disturbance and dysarthria. Computed tomography and magnetic resonance images of the brain revealed a dural-based mass in the left temporal area. Under the impression of a glioblastoma, a resection and an intraoperative squash cytology were done. A necrotic dirty background as well as bluish-to-pinkish myxoid stroma were characteristic; the nuclei of highly pleomorphic tumor cells were hyperchromatic to vesicular with an occasional ground-glass appearance. The cytoplasm was of an eosinophilic hyalinized condensed morphology with an occasional granular appearance. Histologically, the lobulated mass was composed of hypercellular lobules of well-differentiated chondrocytes intermixed with anaplastic pleomorphic cells and diagnosed as a conventional grade III chondrosarcoma. These cells were immunoreactive for D2-40, S-100 protein and vimentin. Brain invasion was also found. Conclusion: Albeit rare, dural-based chondrosarcomas should be considered in the differential diagnosis for meningeal tumors, especially in the case of previous radiation therapy.

scholarly journals Links between Immune Cells from the Periphery and the Brain in the Pathogenesis of Epilepsy: A Narrative Review

2021 ◽  
Vol 22 (9) ◽  
pp. 4395
Author(s):  
Gaku Yamanaka ◽  
Shinichiro Morichi ◽  
Tomoko Takamatsu ◽  
Yusuke Watanabe ◽  
Shinji Suzuki ◽  
...  
Keyword(s):  
Immune Cell ◽  
Genetic Manipulation ◽  
Neurovascular Unit ◽  
Therapeutic Interventions ◽  
Research Directions ◽  
Cerebrovascular Dysfunction ◽  
Central Nervous Systems ◽  
The Central Nervous System ◽  
Time Required ◽  
The Brain

Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction. Peripheral immune cell invasion into the brain, along with these responses, is implicitly involved in epilepsy. This review explored the current literature on the association between the peripheral and central nervous systems in the pathogenesis of epilepsy, and highlights novel research directions for therapeutic interventions targeting these reactions. Previous experimental and human studies have demonstrated the activation of the innate and adaptive immune responses in the brain. The time required for monocytes (responsible for innate immunity) and T cells (involved in acquired immunity) to invade the central nervous system after a seizure varies. Moreover, the time between the leakage associated with blood–brain barrier (BBB) failure and the infiltration of these cells varies. This suggests that cell infiltration is not merely a secondary disruptive event associated with BBB failure, but also a non-disruptive event facilitated by various mediators produced by the neurovascular unit consisting of neurons, perivascular astrocytes, microglia, pericytes, and endothelial cells. Moreover, genetic manipulation has enabled the differentiation between peripheral monocytes and resident microglia, which was previously considered difficult. Thus, the evidence suggests that peripheral monocytes may contribute to the pathogenesis of seizures.

Sign in / Sign up

Export Citation Format

Share Document