Neuron–Glial Interactions in Health and Brain Cancer DOI
Yuan Pan, Michelle Monje

Advanced Biology, Journal Year: 2022, Volume and Issue: 6(9)

Published: Aug. 11, 2022

Abstract Brain tumors are devastating diseases of the central nervous system. tumor pathogenesis depends on both tumor‐intrinsic oncogenic programs and extrinsic microenvironmental factors, including neurons glial cells. Glial cells (oligodendrocytes, astrocytes, microglia) make up half in brain, interact with to modulate neurodevelopment plasticity. Many brain exhibit transcriptomic profiles similar macroglial (oligodendrocytes astrocytes) their progenitors, making them likely subvert existing neuron–glial interactions support pathogenesis. For example, oligodendrocyte precursor cells, a putative glioma cell origin, can form bona fide synapses neurons. Such recently identified gliomas drive pathophysiology, underscoring how take advantage cancer progression. In this review, it is briefly summarized activity normally discussed utilize initiation Unresolved questions these topics potential avenues therapeutically target neuron–glia–cancer also pointed out.

Language: Английский

Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells DOI Creative Commons
Yao Liu, Xi Shen, Yuhan Zhang

et al.

Glia, Journal Year: 2023, Volume and Issue: 71(6), P. 1383 - 1401

Published: Feb. 17, 2023

Abstract The mammalian brain is a complex organ comprising neurons, glia, and more than 1 × 10 14 synapses. Neurons are heterogeneous group of electrically active cells, which form the framework circuitry brain. However, glial primarily divided into astrocytes, microglia, oligodendrocytes (OLs), oligodendrocyte precursor cells (OPCs), constitute approximately half all neural in central nervous system (CNS) mainly provide nutrition tropic support to neurons In last two decades, concept “tripartite synapses” has drawn great attention, emphasizes that astrocytes an integral part synapse regulate neuronal activity feedback manner after receiving signals. Since then, synaptic modulation by been extensively studied substantially revised. this review, we summarize latest significant findings on how particular, microglia OL lineage impact remodel structure function synapses Our review highlights cellular molecular aspects neuron‐glia crosstalk provides additional information aberrant communication between glia may contribute pathologies.

Language: Английский

Citations

72
The role of the complement system in the response to cytotoxic therapy DOI Creative Commons

K Lee,

Qingyang Zhang, Tatsuya Suwa

et al.

Seminars in Immunology, Journal Year: 2025, Volume and Issue: 77, P. 101927 - 101927

Published: Jan. 6, 2025

The complement system is increasingly recognised as a key player in tumour progression and response to cancer treatment. Cytotoxic therapies, including chemo- radiotherapy are standard-of-care for the majority of patients. Cytotoxics have been found alter expression proteins activation components. Many recent reports highlight role local dysregulation microenvironment how targeting such can either anti- or pro-tumoricidal effects depending on several factors treatment scheduling, type its characteristics. This review will explore complex cytotoxic therapy regulation what lessons be learnt identify most effective way therapeutically modulate therapy.

Language: Английский

Citations

2
The Role of Complement in Synaptic Pruning and Neurodegeneration DOI Creative Commons
Ángela Gómez-Arboledas, Munjal M. Acharya, Andrea J. Tenner

et al.

ImmunoTargets and Therapy, Journal Year: 2021, Volume and Issue: Volume 10, P. 373 - 386

Published: Sept. 1, 2021

The complement system, an essential part of the innate immune is composed a group secreted and membrane proteins that collectively participate in maintaining function healthy diseased brain. However, inappropriate activation system has been related to inflammatory response multiple diseases, such as stroke, traumatic brain injury, sclerosis, Alzheimer's disease, well Zika infection radiotherapy. In addition, C1q C3 (initial components cascade) have shown play key beneficial role refinement synaptic circuits during developmental stages adult plasticity. Nevertheless, excessive pruning can be detrimental associated with loss several pathological conditions. this brief review, we will discuss its contribution neurodegeneration cognitive deficits. We also mention potential therapeutic approaches target treat neuroinflammatory diseases unintended consequences

Language: Английский

Citations

97
Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism DOI Creative Commons

Cátia Monteiro,

Lauritz Miarka,

María Perea-García

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 752 - 765

Published: April 1, 2022

Abstract Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and associated toxicity have questioned clinical impact of this approach emphasized need alternative treatments. Given limited therapeutic options available these poor understanding molecular mechanisms underlying resistance metastatic lesions to WBRT, we sought uncover actionable targets biomarkers that could help refine patient selection. Through an unbiased analysis experimental vivo models metastasis resistant identified activation S100A9–RAGE–NF-κB–JunB pathway metastases as a potential mediator organ. Targeting genetically or pharmacologically was sufficient revert WBRT increase benefits at lower doses radiation. In primary melanoma, lung breast adenocarcinoma developing metastasis, endogenous S100A9 levels correlated response underscored blood noninvasive biomarker. Collectively, provide framework personalize improve through combination radiosensitizer balances benefit toxicity.

Language: Английский

Citations

56
BDNF Augmentation Using Riluzole Reverses Doxorubicin-Induced Decline in Cognitive Function and Neurogenesis DOI Creative Commons

Manal T. Usmani,

Robert P. Krattli, Sanad M. El-Khatib

et al.

Neurotherapeutics, Journal Year: 2023, Volume and Issue: 20(3), P. 838 - 852

Published: Jan. 31, 2023

Cancer-related cognitive impairment (CRCI) considerably affects the quality of life millions cancer survivors. Brain-derived neurotrophic factor (BDNF) has been shown to promote survival, differentiation, and maintenance in vivo dentate neurogenesis, chemotherapy induces a plethora physiological cellular alterations, including decline neurogenesis increased neuroinflammation linked with impairments. In our clinical studies, breast patients treated doxorubicin (Adriamycin

Language: Английский

Citations

22
Microglia as Therapeutic Target for Radiation-Induced Brain Injury DOI Open Access
Qun Liu, Huang Yan, Mengyun Duan

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8286 - 8286

Published: July 27, 2022

Radiation-induced brain injury (RIBI) after radiotherapy has become an increasingly important factor affecting the prognosis of patients with head and neck tumor. With delivery high doses radiation to tissue, microglia rapidly transit a pro-inflammatory phenotype, upregulate phagocytic machinery, reduce release neurotrophic factors. Persistently activated mediate progression chronic neuroinflammation, which may inhibit neurogenesis leading occurrence neurocognitive disorders at advanced stage RIBI. Fully understanding microglial pathophysiology cellular molecular mechanisms irradiation facilitate development novel therapy by targeting prevent RIBI subsequent neurological neuropsychiatric disorders.

Language: Английский

Citations

37
The role of the complement system in Multiple Sclerosis: A review DOI Creative Commons
Nil Saez-Calveras, Olaf Stüve

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 10, 2022

The complement system has been involved in the pathogenesis of multiple neuroinflammatory and neurodegenerative conditions. In this review, we evaluated possible role activation sclerosis (MS) with a focus progressive MS, where disease remains to be fully elucidated treatment options are limited. evidence for involvement white matter plaques gray lesions MS stems from immunohistochemical analysis post-mortem brains, vivo serum cerebrospinal fluid biomarker studies, animal models Experimental Autoimmune Encephalomyelitis (EAE). Complement knock-out studies these have revealed that may “double-edge sword” effect MS. On one hand, proteins aid promoting clearance myelin degradation products other debris through myeloid cell-mediated phagocytosis. other, its aberrant lead demyelination at rim as well synapse loss matter. also interact known risk factors including Epstein Barr Virus (EBV) infection, perpetuate CNS self-reactive B cell populations. With mounting development modulating therapies condition is appealing. Herein, reviewed pharmacological inhibitors tested clinical trials neurologic diseases. potential use agents, such C5-binding antibody eculizumab will require detailed understanding different effectors better delivery strategies compounds.

Language: Английский

Citations

28
Uncovering the protective neurological mechanisms of hypofractionated FLASH radiotherapy DOI Creative Commons
Yasaman Alaghband, Barrett D. Allen, Enikö A. Kramár

et al.

Cancer Research Communications, Journal Year: 2023, Volume and Issue: 3(4), P. 725 - 737

Published: March 31, 2023

Implementation of ultra-high dose-rate FLASH radiotherapy (FLASH-RT) is rapidly gaining traction as a unique cancer treatment modality able to dramatically minimize normal tissue toxicity while maintaining antitumor efficacy compared with standard-of-care at conventional dose rate (CONV-RT). The resultant improvements in the therapeutic index have sparked intense investigations pursuit underlying mechanisms. As preamble clinical translation, we exposed non–tumor-bearing male and female mice hypofractionated (3 × 10 Gy) whole brain FLASH- CONV-RT evaluate differential neurologic responses using comprehensive panel functional molecular outcomes over 6-month follow-up. In each instance, extensive rigorous behavioral testing showed FLASH-RT preserve cognitive indices learning memory that corresponded similar protection synaptic plasticity measured by long-term potentiation (LTP). These beneficial were not found after linked preservation integrity (synaptophysin) level reductions neuroinflammation (CD68+ microglia) throughout specific regions known be engaged our selected tasks (hippocampus, medial prefrontal cortex). Ultrastructural changes presynaptic/postsynaptic bouton (Bassoon/Homer-1 puncta) within these same differ response rate. With this clinically relevant dosing regimen, provide mechanistic blueprint from synapse cognition detailing how reduces complications irradiated brain. Significance: Functional LTP are reduction protracted irradiation times.

Language: Английский

Citations

18
Treatment of Radiation‐Induced Brain Necrosis DOI Creative Commons
Xiaojing Yang, Hanru Ren, Jie Fu

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Radiation-induced brain necrosis (RBN) is a serious complication of intracranial as well skull base tumors after radiotherapy. In the past, due to lack effective treatment, radiation was considered be progressive and irreversible. With better understanding in histopathology neuroimaging, occurrence development RBN have been gradually clarified, new treatment methods are constantly emerging. recent years, some scholars tried treat with bevacizumab, nerve growth factor, gangliosides achieved similar results. Some cases can repairable reversible. We aimed summarize incidence, pathogenesis, RBN.

Language: Английский

Citations

40
Cranial irradiation disrupts homeostatic microglial dynamic behavior DOI Creative Commons
Alexandra O. Strohm,

Carl J. Johnston,

Eric Hernady

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: April 3, 2024

Abstract Cranial irradiation causes cognitive deficits that are in part mediated by microglia, the resident immune cells of brain. Microglia highly reactive, exhibiting changes shape and morphology depending on function they performing. Additionally, microglia processes make dynamic, physical contacts with different components their environment to monitor functional state brain promote plasticity. Though evidence suggests radiation perturbs homeostatic functions, it is unknown how cranial impacts dynamic behavior over time. Here, we paired vivo two-photon microscopy a transgenic mouse model labels cortical follow these determine change time irradiated mice control littermates. We show single dose 10 Gy disrupts dynamics during 1-month course. found lasting loss microglial following irradiation, coupled modest dysregulation soma displacement at earlier timepoints. The homogeneous distribution was maintained, suggesting rearrange themselves account for cell maintain territorial organization irradiation. Furthermore, reduced coverage parenchyma surveillance capacity, without overtly changing morphology. Our results demonstrate can induce could influence neurological health. These set foundation future work examining complex cellular which contribute manifestation deficits.

Language: Английский

Citations

5