Journal Description
Neuroglia
Neuroglia
is an international, peer-reviewed, open access journal on Neuroscience published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 24.6 days after submission; acceptance to publication is undertaken in 6 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Journal Clusters-Neurosciences: Brain Sciences, Neurology International, NeuroSci, Clinical and Translational Neuroscience, Neuroglia, Psychiatry International, Clocks & Sleep and Journal of Dementia and Alzheimer's Disease.
Latest Articles
R-Spondin 1 Suppresses Inflammatory Cytokine Production in Human Cortical Astrocytes
Neuroglia 2024, 5(4), 445-451; https://doi.org/10.3390/neuroglia5040028 (registering DOI) - 11 Nov 2024
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Background/Objectives: Wnt signaling pathways are essential in various biological processes, including embryonic development and tissue homeostasis, and are implicated in many diseases. The R-Spondin (RSpo) family, particularly RSpo1, plays a significant role in modulating Wnt signaling. This study aims to explore how RSpo1
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Background/Objectives: Wnt signaling pathways are essential in various biological processes, including embryonic development and tissue homeostasis, and are implicated in many diseases. The R-Spondin (RSpo) family, particularly RSpo1, plays a significant role in modulating Wnt signaling. This study aims to explore how RSpo1 binding to astrocytic LGR6 receptors influences central nervous system (CNS) homeostasis, particularly in the context of inflammation. Methods: Human-induced pluripotent stem cell-derived astrocytes were treated with RSpo1 to assess its impact on inflammatory cytokine release. A proteomic analysis was conducted using a Human Cytokine Array Kit to measure differential protein expression. Pathway enrichment analysis was performed to identify affected signaling pathways. Results: RSpo1 treatment led to a suppression of inflammatory cytokines such as IL-10, IFN-γ, and IL-23 in astrocytes, while TNF-α and CXCL12 levels were increased. Pathway analysis revealed significant alterations in key signaling pathways, including cytokine–cytokine receptor interaction, chemokine signaling, and TNF signaling pathways, suggesting RSpo1’s role in modulating immune responses within the CNS. Conclusions: RSpo1 significantly influences inflammatory responses in astrocytes by modulating cytokine release and altering key signaling pathways. These findings enhance our understanding of the interaction between cell-specific Wnt signaling and CNS inflammation, suggesting potential therapeutic applications of RSpo1 in neuroinflammatory and neurodegenerative diseases.
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Open AccessReview
The Alteration of Microglial Calcium Homeostasis in Central Nervous System Disorders: A Comprehensive Review
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Al Riyad Hasan, Faria Tasnim, Md. Aktaruzzaman, Md. Tarikul Islam, Rifat Rayhan, Afrina Brishti, Junguk Hur, James E. Porter and Md. Obayed Raihan
Neuroglia 2024, 5(4), 410-444; https://doi.org/10.3390/neuroglia5040027 - 21 Oct 2024
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Microglia, the unique and motile immune cells of the central nervous system (CNS), function as a security guard in maintaining CNS homeostasis, primarily through calcium signaling. The calcium dynamics in microglia control important functions such as phagocytosis, cytokine release, and migration. Calcium dysregulation
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Microglia, the unique and motile immune cells of the central nervous system (CNS), function as a security guard in maintaining CNS homeostasis, primarily through calcium signaling. The calcium dynamics in microglia control important functions such as phagocytosis, cytokine release, and migration. Calcium dysregulation in microglia has been linked to several CNS disorders, like Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and ischemic stroke (IS). Calcium entering through channels such as voltage-gated calcium channels (VGCCs), store-operated calcium entry (SOCE), and transient receptor potential (TRP) channels is essential for microglial activation and pro-inflammatory responses. Under pathological conditions, like the formation of amyloid-β plaques in AD, aggregation of α-synuclein in PD, and oxidative stress in MS, calcium dysregulation exacerbates neuroinflammation, mitochondrial dysfunction, and neurodegeneration. Therapeutic strategies targeting calcium signaling pathways, using calcium channel blockers and antioxidant interventions, show promise for alleviating microglial activation and slowing down disease progression. This review summarizes the underlying mechanisms of microglial calcium dysregulation and potential therapeutic benefits for restoring microglial calcium balance in CNS disorders.
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Open AccessReview
Harnessing Mitophagy for Therapeutic Advances in Aging and Chronic Neurodegenerative Diseases
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Devlina Ghosh and Alok Kumar
Neuroglia 2024, 5(4), 391-409; https://doi.org/10.3390/neuroglia5040026 - 15 Oct 2024
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Introduction: Mitophagy, the selective degradation of damaged mitochondria, is essential for maintaining cellular health and function, particularly in high-energy demanding post-mitotic cells like neurons and in microglial cells. Aging results in impaired mitophagy, leading to mitochondrial dysfunction, oxidative stress, the release of damage-associated
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Introduction: Mitophagy, the selective degradation of damaged mitochondria, is essential for maintaining cellular health and function, particularly in high-energy demanding post-mitotic cells like neurons and in microglial cells. Aging results in impaired mitophagy, leading to mitochondrial dysfunction, oxidative stress, the release of damage-associated proteins (DAMPs), and neuroinflammation, which contribute to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Mitochondrial dysfunction also contributes to the pathophysiology of depression by affecting synaptic plasticity, increasing neuroinflammation, and heightening oxidative stress. Aim: In this review, we summarize the recent developments on mechanisms of mitophagy, its therapeutic role in neuroprotection, and its implications in aging and neuroinflammation, complemented by future research requirements and implications. Result/Discussion: Therapeutic strategies that promote mitochondrial health, including enhancing mitophagy and mitochondrial biogenesis, show promise in treating neurodegenerative diseases and depression. Recent findings have emphasized therapeutic strategies to modulate mitophagy, such as pharmacological agents like urolithin A and rapamycin, genetic interventions such as PINK1/Parkin gene therapy, mitochondrial transplantation, and lifestyle and dietary interventions such as caloric restriction, exercise, and dietary supplements such as resveratrol and CoQ10. Key regulators of mitophagy, including the PINK1/Parkin pathway and various proteins like BNIP3, NIX, and FUNDC1, which facilitate the removal of damaged mitochondria, play a crucial role. Conclusions: These results highlight the importance of understanding the interplay between mitophagy and neuroinflammation and show that modulation of mitophagy can reduce oxidative stress and improve neuroinflammatory outcomes and depression in age-related neurodegenerative diseases. However, despite significant progress, challenges remain in understanding the underlying molecular mechanisms of mitophagy and its therapeutic regulation in aging disorders.
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Open AccessReview
Imaging Recommendations for Diagnosis, Staging, and Management of Primary Central Nervous System Neoplasms in Adults
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Kajari Bhattacharya and Abhishek Mahajan
Neuroglia 2024, 5(4), 370-390; https://doi.org/10.3390/neuroglia5040025 - 1 Oct 2024
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Central nervous system (CNS) neoplasms are a vast and diverse group of tumors in adults with variable prognoses depending on histology and increasingly understood molecular features. There has been a major paradigm shift in the approach towards these neoplasms ever since the implications
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Central nervous system (CNS) neoplasms are a vast and diverse group of tumors in adults with variable prognoses depending on histology and increasingly understood molecular features. There has been a major paradigm shift in the approach towards these neoplasms ever since the implications of these molecular features have been recognized. Gliomas are the major group of primary CNS neoplasms in adults, and glioblastomas are a significant cause of morbidity and mortality, especially in older patients. Apart from gliomas, meningiomas and pituitary tumors are other major groups. This review aims to elucidate the role of imaging in the screening, diagnosis, management, and follow-up of major primary CNS neoplasms, with an elaborate discussion on the role of artificial intelligence and advanced imaging techniques and future directions likely to play a pivotal role in this ever-evolving subspecialty of oncology.
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Open AccessReview
Biomarkers of Acute Brain Injury
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Konstantinos Barmpagiannos, Nikolaos Lazaridis, Aikaterini Apostolopoulou and Barbara Fyntanidou
Neuroglia 2024, 5(4), 356-369; https://doi.org/10.3390/neuroglia5040024 - 1 Oct 2024
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Introduction: Acute brain injury is one of the most important causes of morbidity, mortality and disability worldwide. Time is the most important aspect of acute brain injury management. In this context, biomarkers could mitigate the limitations of neuroimaging. Neuro-biomarkers could be used both
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Introduction: Acute brain injury is one of the most important causes of morbidity, mortality and disability worldwide. Time is the most important aspect of acute brain injury management. In this context, biomarkers could mitigate the limitations of neuroimaging. Neuro-biomarkers could be used both to diagnose intracranial pathology and to predict the effectiveness of treatment applications. Aim: The aim of this review is to describe the role of various and specific markers of brain damage with particular emphasis on acute brain injury and stroke. Results/discussion: The diagnostic and prognostic value of modern biomarkers remains relatively questionable, although grouping biomarkers into panels is improving their usefulness. The groups of biomarkers that will be analyzed include astrocytic, axonal, neuronal as well as extracellular biomarkers. Conclusion: Future studies will demonstrate the utility of neuro-biomarkers in the diagnosis, prognosis and therapeutic monitoring of patients with acute brain injury in the intensive care unit.
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Open AccessArticle
High-Impact AMPAkines Elevate Calcium Levels in Cortical Astrocytes by Mobilizing Endoplasmic Reticular Calcium Stores
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Daniel P. Radin, Rok Cerne, Jeffrey Witkin and Arnold Lippa
Neuroglia 2024, 5(3), 344-355; https://doi.org/10.3390/neuroglia5030023 - 9 Sep 2024
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Ampakines—positive allosteric modulators of AMPA-type glutamate receptors (AMPARs)—are drug candidates that have shown substantial promise in pre-clinical models of various neurodegenerative and neuropsychiatric diseases. Much of the study of ampakines has focused on how these drugs modulate neuronal AMPARs to achieve certain therapeutic
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Ampakines—positive allosteric modulators of AMPA-type glutamate receptors (AMPARs)—are drug candidates that have shown substantial promise in pre-clinical models of various neurodegenerative and neuropsychiatric diseases. Much of the study of ampakines has focused on how these drugs modulate neuronal AMPARs to achieve certain therapeutic effects. However, astrocytes also express functional AMPARs and their physiology may be sensitive to modulation by ampakines. Herein, we investigate the effects of multiple ampakines on calcium levels in cortical astrocytes. We find that ampakines augment cytosolic calcium elevations in astrocytes to an extent far greater than that achieved by AMPA alone. This effect is amenable to competitive AMPAR blockade. Furthermore, calcium induction is sensitive to phospholipase Cβ antagonism and blockade of inositol triphosphate receptors located on the endoplasmic reticulum. Low-impact ampakines exerted weaker effects on cytosolic calcium levels in astrocytes and higher concentrations were required to observe an effect. Furthermore, high doses of the low-impact ampakine, CX717, were not toxic to cortical astrocytes at high concentrations, which may serve to differentiate low-impact ampakines from classical AMPAR positive modulators like cyclothiazide. As ampakines are further developed for clinical use, it would be prudent to determine the extent to and manner by which they affect astrocytes, as these effects may also underpin their therapeutic utility in CNS pathologies.
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Open AccessArticle
Functional Glial Activation Mediates Phenotypic Effects of APOEɛ4 and Sex in Alzheimer’s Disease
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Roger M. Lane, Dan Li and Taher Darreh-Shori
Neuroglia 2024, 5(3), 323-343; https://doi.org/10.3390/neuroglia5030022 - 5 Sep 2024
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Background: This study examined the impact of apolipoprotein ɛ4 (APOEɛ4) allele frequency and sex on the phenotype of Alzheimer’s disease (AD). Methods: This post hoc study evaluated the baseline characteristics, cerebrospinal fluid (CSF) and neuroimaging biomarkers, and cognition scores collected from
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Background: This study examined the impact of apolipoprotein ɛ4 (APOEɛ4) allele frequency and sex on the phenotype of Alzheimer’s disease (AD). Methods: This post hoc study evaluated the baseline characteristics, cerebrospinal fluid (CSF) and neuroimaging biomarkers, and cognition scores collected from 45 patients aged 50–74 years with CSF-biomarker-confirmed mild cognitive impairment or mild dementia due to AD from clinical trial NCT03186989. Results: A phenotypic spectrum was observed from a predominant amyloid and limbic–amnestic phenotype in male APOEɛ4 homozygotes to a predominantly tau, limbic-sparing, and multidomain cognitive impairment phenotype in female APOEɛ4 noncarriers. Amyloid pathology was inversely correlated with tau pathophysiology, glial activation, and synaptic injury, with the strongest associations observed in male APOEɛ4 carriers. Tau pathophysiology was correlated with glial activation, synaptic injury, and neuroaxonal damage, with the strongest correlation observed in female APOEɛ4 noncarriers. Conclusions: These data support the hypothesis that functional glial activation is influenced by apoE isoform and sex and might explain much of the biological and clinical heterogeneity in early clinical AD in those aged 50–74 years. Conclusions are limited because of the retrospective nature and small sample size. Trial Registration: Clinical Trial NCT03186989.
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Open AccessArticle
Impacts of Electroconvulsive Therapy on the Neurometabolic Activity in a Mice Model of Depression: An Ex Vivo 1H-[13C]-NMR Spectroscopy Study
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Ajay Sarawagi, Pratishtha Wadnerkar, Vrundika Keluskar, Narra Sai Ram, Jerald Mahesh Kumar and Anant Bahadur Patel
Neuroglia 2024, 5(3), 306-322; https://doi.org/10.3390/neuroglia5030021 - 2 Sep 2024
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Electroconvulsive therapy (ECT) is an effective treatment for severe and drug-resistant depression, yet its mode of action remains poorly understood. This study aimed to evaluate the effects of ECT on neurometabolism using ex vivo 1H-[13C]-NMR spectroscopy in conjunction with intravenous
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Electroconvulsive therapy (ECT) is an effective treatment for severe and drug-resistant depression, yet its mode of action remains poorly understood. This study aimed to evaluate the effects of ECT on neurometabolism using ex vivo 1H-[13C]-NMR spectroscopy in conjunction with intravenous infusion of [1,6-13C2]glucose in a chronic variable mild stress (CVMS) model of depression. Both CVMS and control mice were subjected to seven sessions of electroconvulsive shock under mild isoflurane anesthesia. The CVMS mice exhibited a reduction in sucrose preference (CVMS 67.1 ± 14.9%, n = 5; CON 86.5 ± 0.6%, n = 5; p = 0.007), and an increase in immobility duration (175.9 ± 22.6 vs. 92.0 ± 23.0 s, p < 0.001) in the forced-swim test. The cerebral metabolic rates of glucose oxidation in glutamatergic (CMRGlc(Glu)) (CVMS 0.134 ± 0.015 µmol/g/min, n = 5; CON 0.201 ± 0.045 µmol/g/min, n = 5; padj = 0.04) and GABAergic neurons (CMRGlc(GABA)) (0.030 ± 0.002 vs. 0.046 ± 0.011 µmol/g/min, padj = 0.04) were reduced in the prefrontal cortex (PFC) of CVMS mice. ECT treatment in CVMS mice normalized sucrose preference [F(1,27) = 0.0024, p = 0.961] and immobility duration [F(1,28) = 0.434, p = 0.515], but not the time spent in the center zone (CVMS + ECT 10.4 ± 5.5 s, CON + sham 22.3 ± 11.4 s, padj = 0.0006) in the open field test. The ECT-treated CVMS mice exhibited reduced (padj = 0.021) CMRGlc(Glu) in PFC (0.169 ± 0.026 µmol/g/min, n = 8) when compared with CVMS mice, which underwent the sham procedure (0.226 ± 0.030 µmol/g/min, n = 8). These observations are consistent with ECT’s anticonvulsant hypothesis for its anti-depressive action.
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Open AccessArticle
Ethanol Exacerbates the Alzheimer’s Disease Pathology in the 5xFAD Mouse Model
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Hassan E. Mohammed, James C. Nelson and S. Alex Marshall
Neuroglia 2024, 5(3), 289-305; https://doi.org/10.3390/neuroglia5030020 - 2 Aug 2024
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Alzheimer’s disease (AD) is the most common form of dementia with characteristic biological markers. Clinically, AD presents as declines in memory, reasoning, and decision making, but the loss of memory is particularly associated with hippocampal damage. Likewise, excessive ethanol consumption has been found
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Alzheimer’s disease (AD) is the most common form of dementia with characteristic biological markers. Clinically, AD presents as declines in memory, reasoning, and decision making, but the loss of memory is particularly associated with hippocampal damage. Likewise, excessive ethanol consumption has been found to disrupt hippocampal function and integrity. To assess the potential shared consequences of AD pathology and ethanol, 5xFAD mice were administered 5 g/kg ethanol daily for 10 days. Immunohistochemical analysis revealed ethanol and AD converged to lead to microglial and astrocytic senescence as well as increased Aß-plaque formation in the hippocampus. Despite the exacerbation of these potential mechanisms of neurodegeneration, there were no additive effects of ethanol exposure and AD-related genotype on Fluoro-Jade C (FJC)+ cells or cognitive deficits in the novel object recognition task. Overall, these results are the first to characterize the effects of ethanol exposure on early adulthood in the 5xFAD mouse model. Together these findings support the idea that alcohol can influence AD pathology; however, the mechanisms involved in AD progression (e.g., glial activation and Aß-plaque) may be impacted prior to evidence of pathology (e.g., cognitive decline or neuronal loss).
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Open AccessReview
Sexual Dimorphism and Hypothalamic Astrocytes: Focus on Glioprotection
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Natalie K. Thomaz, Larissa Daniele Bobermin and André Quincozes-Santos
Neuroglia 2024, 5(3), 274-288; https://doi.org/10.3390/neuroglia5030019 - 2 Aug 2024
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Sexual dimorphism refers to biological differences between males and females in the same species, including morphological, physiological, and behavioral characteristics. Steroid hormones are associated with changes in several brain regions, as well as the pathophysiology of aging, obesity, and neuropsychiatric diseases. The hypothalamus
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Sexual dimorphism refers to biological differences between males and females in the same species, including morphological, physiological, and behavioral characteristics. Steroid hormones are associated with changes in several brain regions, as well as the pathophysiology of aging, obesity, and neuropsychiatric diseases. The hypothalamus controls several physiological processes, including metabolism, reproduction, circadian rhythm, and body homeostasis. Refined communication between neurons and glial cells, particularly astrocytes, coordinates physiological and behavioral hypothalamic functions. Therefore, from previously published studies, this review aims to highlight sex-related differences in rodent hypothalamic astrocytes, since we believe that this brain region is essential for the understanding of dimorphic patterns that are influenced by steroid sex hormones. Thus, we review concepts of sexual dimorphism, the hypothalamic-pituitary-gonadal axis, the role of hormonal influence on hypothalamic astrocyte functions, neuroglial communication, as well as sexual dimorphism and neuropsychiatric disorders and glioprotective mechanisms associated with the hypothalamus.
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Open AccessReview
The Gut Microbiome-Neuroglia Axis: Implications for Brain Health, Inflammation, and Disease
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Josué Camberos-Barraza, Alma M. Guadrón-Llanos and Alberto K. De la Herrán-Arita
Neuroglia 2024, 5(3), 254-273; https://doi.org/10.3390/neuroglia5030018 - 1 Aug 2024
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The human central nervous system is convolutedly connected to the gut microbiome, a diverse community of microorganisms residing in the gastrointestinal tract. Recent research has highlighted the bidirectional communication between the gut microbiome and neuroglial cells, which include astrocytes, microglia, oligodendrocytes, and ependymal
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The human central nervous system is convolutedly connected to the gut microbiome, a diverse community of microorganisms residing in the gastrointestinal tract. Recent research has highlighted the bidirectional communication between the gut microbiome and neuroglial cells, which include astrocytes, microglia, oligodendrocytes, and ependymal cells. These neuroglial cells are essential for maintaining CNS homeostasis, supporting neuronal function, and responding to pathological conditions. This review examines the interactions between the gut microbiome and neuroglia, emphasizing their critical roles in brain health and the development of neurological disorders. Dysbiosis, or imbalance in the gut microbiome, has been associated with various neurological and psychiatric conditions, such as autism spectrum disorder, anxiety, depression, and neurodegenerative diseases like Alzheimer’s and Parkinson’s. The microbiome influences brain function through microbial metabolites, immune modulation, and neuroinflammatory responses. Understanding these interactions paves the way for new therapeutic targets and strategies for preventing and treating CNS disorders. This scoping review aims to highlight the mechanisms of the microbiome-neuroglia axis in maintaining brain health and its potential as a therapeutic target.
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Open AccessReview
The Neuroimmunological Nexus of Multiple Sclerosis: Deciphering the Microglial Transcriptomic Tapestry
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Akanksha Jha and Hemant Kumar
Neuroglia 2024, 5(3), 234-253; https://doi.org/10.3390/neuroglia5030017 - 20 Jul 2024
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Microglia are poorly understood immune cells of the central nervous system that play a determining role in the progression of multiple sclerosis. With the advent of genomic techniques such as single-cell RNA sequencing and single-nucleus RNA sequencing, a more comprehensive understanding of microglia
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Microglia are poorly understood immune cells of the central nervous system that play a determining role in the progression of multiple sclerosis. With the advent of genomic techniques such as single-cell RNA sequencing and single-nucleus RNA sequencing, a more comprehensive understanding of microglia at the transcriptomic level has uncovered various disease-specific clusters, context-dependent heterogeneity, and region-specific microglia, unlocking the recondite secrets embedded within these glial cells. These techniques have raised questions regarding the conventional and widely accepted categorization of microglia as M1 and M2 phenotypes. The neuroimmune component of multiple sclerosis, which is the microglia, makes it a complex and challenging disease. This review aims to demystify the complexities of microglia in multiple sclerosis, providing a vivid map of different clusters and subclusters of microglia found in multiple sclerosis and outlining the current knowledge of the distinctive roles of microglia. Also, this review highlights the neuroimmune interaction with microglia as the epicenter and how they act as sabotaging agents. Moreover, this will provide a more comprehensive direction toward a treatment approach focusing on local, region-specific microglia.
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Open AccessOpinion
Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma
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Richard E. Kast
Neuroglia 2024, 5(3), 223-233; https://doi.org/10.3390/neuroglia5030016 - 2 Jul 2024
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Glioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason current treatments almost always
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Glioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason current treatments almost always fail. Stopping bradykinin-triggered migration would be a step closer to control of this disease. The recent approval and marketing of an oral plasma kallikrein inhibitor, berotralstat (Orladeyo™), and pending FDA approval of a similar drug, sebetralstat, now offers a potential method for reducing local bradykinin production at sites of bradykinin-mediated glioblastoma migration. Both drugs are approved for treating hereditary angioedema. They are ideal for repurposing as a treatment adjunct in glioblastoma. Furthermore, it has been established that peritumoral edema, a common problem during the clinical course of glioblastoma, is generated in large part by locally produced bradykinin via kallikrein action. Both brain edema and the consequent use of corticosteroids both shorten survival in glioblastoma. Therefore, by (i) migration inhibition, (ii) growth inhibition, (iii) edema reduction, and (iv) the potential for less use of corticosteroids, berotralstat may be of service in treatment of glioblastoma, slowing disease progression. This paper recounts the details and past research on bradykinin in glioblastoma and the rationale of treating it with berotralstat.
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(This article belongs to the Special Issue Glioblastoma (GBM) Brain Tumor Invasion and Consequences on Diagnosis, Clinical Strategies and Therapy)
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Open AccessArticle
Xc- System as a Possible Target for ConBr Lectin Interaction in Glioma Cells
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Vanir Reis Pinto-Junior, Rodrigo Lopes Seeger, Cláudio Henrique Dahne Souza-Filho, Angela Patricia França, Nicole Sartori, Messias Vital Oliveira, Vinicius Jose Silva Osterne, Kyria Santiago Nascimento, Rodrigo Bainy Leal and Benildo Sousa Cavada
Neuroglia 2024, 5(3), 202-222; https://doi.org/10.3390/neuroglia5030015 - 1 Jul 2024
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Studies have revealed the dependence of glioma cells on iron, making them sensitive to ferroptosis. Ferroptosis can be triggered by inhibition of the xc- system, resulting in redox imbalance and membrane lipid peroxidation. The xc- system is composed of two coupled proteins, xCT
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Studies have revealed the dependence of glioma cells on iron, making them sensitive to ferroptosis. Ferroptosis can be triggered by inhibition of the xc- system, resulting in redox imbalance and membrane lipid peroxidation. The xc- system is composed of two coupled proteins, xCT and CD98hc. The control of transporters, such as xCT, by the CD98hc glycoprotein suggests that molecules targeting glycans may have an impact on the treatment of glioma. This study evaluated the effect of the Canavalia brasiliensis (ConBr) lectin on C6 glioma cells and compared it with erastin, an xc- system inhibitor. Both induced dose-dependent cell death, accompanied by an increase in the production of reactive oxygen species and a decrease in reduced glutathione. However, co-treatment did not show an additive effect. The analysis was updated by molecular dynamics assessments of the xc- system interacting with ConBr or erastin. The interaction of erastin with the xc- system affects its interaction with ConBr, reducing the antagonistic effect when both are in the protein complex. The data show that ConBr is effective in inducing cell death in glioma cells and regulates the xc system through interaction with CD98hc glycans, showing that lectins have the potential to promote ferroptosis in glioma cells.
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Open AccessArticle
Telmisartan Reduces LPS-Mediated Inflammation and Induces Autophagy of Microglia
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Kwame O. Affram, Zachary C. Janatpour, Nagesh Shanbhag, Sonia Villapol and Aviva J. Symes
Neuroglia 2024, 5(2), 182-201; https://doi.org/10.3390/neuroglia5020014 - 20 Jun 2024
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Background: Chronic neuroinflammation mediated by persistent microglial activation is strongly linked to neurodegeneration. Therefore, targeting microglial activation could be beneficial in treating neurodegenerative disorders. Angiotensin receptor blockers (ARBs), commonly prescribed for high blood pressure, exhibit prominent anti-inflammatory effects in the brain and are
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Background: Chronic neuroinflammation mediated by persistent microglial activation is strongly linked to neurodegeneration. Therefore, targeting microglial activation could be beneficial in treating neurodegenerative disorders. Angiotensin receptor blockers (ARBs), commonly prescribed for high blood pressure, exhibit prominent anti-inflammatory effects in the brain and are considered potential therapies for neurodegenerative diseases and neurotrauma. Although all ARBs are angiotensin II receptor type I antagonists, some ARBs act through other signaling pathways, allowing for multiple mechanisms of action. The anti-inflammatory mechanisms of ARBs are not well understood. Methods: In this study, we compared eight different FDA-approved ARBs for their ability to reduce the LPS stimulation of primary microglia or BV2 cells through analyses of nitric oxide production, reactive oxygen species generation, and the mRNA of proinflammatory cytokines. Finding specific and unique effects of telmisartan, we interrogated signaling pathways and other downstream effectors of telmisartan activity on microglia. Results: Our findings indicate that telmisartan showed the greatest efficacy in reducing the LPS induction of reactive oxygen species (ROS) and nitric oxide production in microglia. Uniquely amongst ARBs, telmisartan activated AMPK phosphorylation and inhibited mTOR phosphorylation. Telmisartan’s anti-inflammatory activity was partially inhibited by the AMPK inhibitor compound C. Furthermore, telmisartan uniquely induced markers of autophagy in microglia through an AMPK–mTOR–autophagy pathway. Telmisartan also reduced microglial viability. Telmisartan’s cytotoxicity was partially ameliorated by an autophagy inhibitor and a pan-caspase inhibitor, indicating a link between microglial autophagy and apoptosis. Conclusions: We conclude that telmisartan has unique properties relative to other ARBs, including potent anti-inflammatory actions and an induction of microglial autophagy, which may enable specific therapeutic uses.
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Open AccessReview
Left-Parietal Angiocentric Glioma: Our Experience and a Review of the Literature
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Antonello Curcio, Shervin Espahbodinea, Eva Azzurra Li Trenta, Rosamaria Ferrarotto, Aristide Nanni, Noemi Arabia, Giorgio Ciccolo, Giovanni Raffa, Francesca Granata and Antonino Germanò
Neuroglia 2024, 5(2), 165-181; https://doi.org/10.3390/neuroglia5020013 - 1 Jun 2024
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Background: Angiocentric glioma (AG) is a rare, benign, and slow-growing tumor. First described in 2005, it is now gaining attention with respect to the possibility of being diagnosed. Even with no statistical differences between sex, it has been reported both in children and
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Background: Angiocentric glioma (AG) is a rare, benign, and slow-growing tumor. First described in 2005, it is now gaining attention with respect to the possibility of being diagnosed. Even with no statistical differences between sex, it has been reported both in children and the elderly. A total of 120 cases have been described in the literature. The aim of this study is to provide new data for a new statistical assessment of the prevalence and incidence of AG in populations. Case report: An 8-year-old male patient with no history of epilepsy and no need for antiepileptic therapy underwent surgery for a left-parietal brain lesion, revealed through MRI. Imaging was acquired after his first absence episode. The lesion was completely resected. Histological findings indicated angiocentric glioma. No signs of recurrency after two years of follow-up. Conclusion: AG is usually an epilepsy-related low-grade glioma. Few cases exhibit disease progression and exitus. Surgical management should aim for a gross total resection to avoid recurrence and persisting epilepsy. Surgery represents the gold standard in diagnosis and treatment and must be performed as soon as possible in consideration of its healing properties and its useful diagnosis.
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Open AccessReview
How Schwann Cells Are Involved in Brain Metastasis
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JuliAnne Allgood, Avery Roe and Jessica E. Pullan
Neuroglia 2024, 5(2), 155-164; https://doi.org/10.3390/neuroglia5020012 - 1 Jun 2024
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The current lack of a comprehensive understanding of brain metastasis mechanisms presents a significant gap in cancer research. This review outlines the role that Schwann cells (SCs) have in this process. SCs are already known for their role in myelination and nerve repair
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The current lack of a comprehensive understanding of brain metastasis mechanisms presents a significant gap in cancer research. This review outlines the role that Schwann cells (SCs) have in this process. SCs are already known for their role in myelination and nerve repair within the peripheral nervous system (PNS), but there is less information on their function in facilitating the transport and activation of neoplastic cells to aid in the invasion of the blood–brain barrier and brain. Detailed insights into SCs’ interactions with various cancers, including lung, breast, melanoma, colon, kidney, and pancreatic cancers, reveal how these cells are coerced into repair-like phenotypes to accelerate cancer spread and modulate immune responses. By outlining SCs’ involvement in perineural invasion and BBB modification, this review highlights their functions in facilitating brain metastasis.
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Open AccessArticle
Prediction of Glioma Resistance to Immune Checkpoint Inhibitors Based on Mutation Profile
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Guillaume Mestrallet
Neuroglia 2024, 5(2), 145-154; https://doi.org/10.3390/neuroglia5020011 - 27 May 2024
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Glioma, a highly aggressive cancer, presents a daunting prognosis, with only 5% of glioblastoma patients surviving beyond five years post diagnosis. Current therapeutic strategies, including surgical intervention, radiotherapy, chemotherapy, and immune checkpoint blockade (ICB), while promising, often encounter limited efficacy, particularly in glioblastoma
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Glioma, a highly aggressive cancer, presents a daunting prognosis, with only 5% of glioblastoma patients surviving beyond five years post diagnosis. Current therapeutic strategies, including surgical intervention, radiotherapy, chemotherapy, and immune checkpoint blockade (ICB), while promising, often encounter limited efficacy, particularly in glioblastoma cases. Addressing this challenge requires a proactive approach to anticipate treatment response and resistance. In this study, we analyzed 117 glioma patients who underwent ICB treatment to uncover the mechanisms underlying treatment resistance. Through a meticulous examination of mutational profiles post ICB, we identified several mutations associated with varied survival outcomes. Notably, mutations such as STAG2 Missense, EGFR A289V Missense, TP53 Nonsense, and RB1 FS del were linked to prolonged overall survival, while others, including IF del, FAT1 E1206Tfs*4 FS del, PDGFRA FS del, PIK3R1 M326Vfs*6 FS del, Y463* Nonsense, NF1 Missense, and R1534*, were associated with poorer survival post ICB. Leveraging these insights, we employed machine learning algorithms to develop predictive models. Remarkably, our model accurately forecasted glioma patient survival post ICB within an error of 4 months based on their distinct mutational profiles. In conclusion, our study advocates for personalized immunotherapy approaches in glioma patients. By integrating patient-specific attributes and computational predictions, we present a promising avenue for optimizing clinical outcomes in immunotherapy.
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Open AccessArticle
Flow Cytometry Characterization and Analysis of Glial and Immune Cells from the Spinal Cord
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Lilian de Oliveira Coser, Manuela Tosi Comelis, Débora Elisa da Costa Matoso, Luciana Politti Cartarozzi and Alexandre Leite Rodrigues de Oliveira
Neuroglia 2024, 5(2), 129-144; https://doi.org/10.3390/neuroglia5020010 - 20 May 2024
Cited by 1
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Several protocols have been developed with the aim of characterizing glial and immune cells from the central and peripheral nervous systems. However, a small number of these protocols have demonstrated the ability to yield satisfactory results following conventional isolation. Considering this necessity and
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Several protocols have been developed with the aim of characterizing glial and immune cells from the central and peripheral nervous systems. However, a small number of these protocols have demonstrated the ability to yield satisfactory results following conventional isolation. Considering this necessity and the difficulties encountered in enzymatic and bead isolation, our work proposes a method for the isolation of glial and immune cells from the spinal cord utilizing a Percoll gradient. For this purpose, C57BL/6J spinal cords were dissected, and the lumbar intumescence was dissociated and subjected to a Percoll gradient centrifugation (70%, 50%, 37%, and 10%). Each layer was then separated and labeled for astrocytes (anti-GFAP, TNF-α, IFN-γ, IL-10, IL-4), microglia (anti-CD45, CD11b, CD206, CD68, TNF-α, IFN-γ), and lymphocytes (anti-CD3, CD4, IFN-γ, IL-4). The gate detections were mathematically performed by computational analysis utilizing the K-means clustering algorithm. The results demonstrated that astrocytes were concentrated at the Percoll 10/37 interface, microglia at the Percoll 37/50 layer, and lymphocytes at the Percoll 50/70 layer. Our findings indicate that astrocytes in healthy animals are putative of the A1 profile, while microglia and lymphocytes are more frequently labeled with M1 and Th1 markers, suggesting a propensity towards inflammatory responses. The computational method enabled the semi-autonomous gate detection of flow cytometry data, which might facilitate and expedite the processing of large amounts of data.
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Open AccessReview
Microglial Dyshomeostasis: A Common Substrate in Neurodevelopmental and Neurodegenerative Diseases
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Vada Andree Furlan, Daria MacAuslan, Khiem Ha, Nitish Patel, Shawn Adam, Beylem Zanagar and Sharmila Venugopal
Neuroglia 2024, 5(2), 119-128; https://doi.org/10.3390/neuroglia5020009 - 12 May 2024
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Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are clinically distinct, yet share synaptic dysfunction as a common brain pathophysiology. Neurodegenerative diseases such as Huntington’s disease (HD) entail a neuroinflammatory cascade of molecular and cellular events which can
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Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are clinically distinct, yet share synaptic dysfunction as a common brain pathophysiology. Neurodegenerative diseases such as Huntington’s disease (HD) entail a neuroinflammatory cascade of molecular and cellular events which can contribute to the death of neurons. Emerging roles for supportive glial cells such as microglia and astrocytes in the ongoing regulation of neural synapses and brain excitability raise the possibility that some of the synaptic pathology and/or inflammatory events could be a direct consequence of malfunctioning glial cells. Focusing on microglia, we cross-examined 12 recently published studies in which microglial dysfunction was induced/identified in a cell-autonomous manner and its functional consequence on neural development, brain volume, functional connectivity, inflammatory response and synaptic regulation were evaluated; in many cases, the onset of symptoms relevant to all three neurodevelopmental disorders were assessed behaviorally. Challenging the classic notion of microglial activation as an inflammatory response to neuropathology, our compilation clarifies that microglial dyshomeostasis itself can consequently disrupt neural homeostasis, leading to neuropathology and symptom onset. This further warranted defining the molecular signatures of context-specific microglial pathology relevant to human diseases.
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