scholarly journals Microglial Cell Morphology and Phagocytic Activity Are Critically Regulated by the Neurosteroid Allopregnanolone: A Possible Role in Neuroprotection

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 698
Author(s):  
Valérie Jolivel ◽  
Susana Brun ◽  
Fabien Binamé ◽  
Jérémie Benyounes ◽  
Omar Taleb ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Phagocytic Activity ◽  
Microglial Cell ◽  
Neurological Diseases ◽  
Time Lapse ◽  
Microglial Cells ◽  
Primary Microglia ◽  
Gaba A ◽  
Neuroprotective Strategies ◽  
Underlying Mechanisms

Microglial cells are key players in neural pathogenesis and microglial function regulation appears to be pivotal in controlling neuroinflammatory/neurological diseases. Here, we investigated the effects and mechanism of action of neurosteroid allopregnanolone (ALLO) on murine microglial BV-2 cells and primary microglia in order to determine ALLO-induced immunomodulatory potential and to provide new insights for the development of both natural and safe neuroprotective strategies targeting microglia. Indeed, ALLO-treatment is increasingly suggested as beneficial in various models of neurological disorders but the underlying mechanisms have not been elucidated. Therefore, the microglial cells were cultured with various serum concentrations to mimic the blood-brain-barrier rupture and to induce their activation. Proliferation, viability, RT-qPCR, phagocytosis, and morphology analyzes, as well as migration with time-lapse imaging and quantitative morphodynamic methods, were combined to investigate ALLO actions on microglia. BV-2 cells express subunits of GABA-A receptor that mediates ALLO activity. ALLO (10µM) induced microglial cell process extension and decreased migratory capacity. Interestingly, ALLO modulated the phagocytic activity of BV-2 cells and primary microglia. Our results, which show a direct effect of ALLO on microglial morphology and phagocytic function, suggest that the natural neurosteroid-based approach may contribute to developing effective strategies against neurological disorders that are evoked by microglia-related abnormalities.

scholarly journals Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Toru Murakawa-Hirachi ◽  
Yoshito Mizoguchi ◽  
Masahiro Ohgidani ◽  
Yoshinori Haraguchi ◽  
Akira Monji
Keyword(s):  
Neuronal Death ◽  
Phagocytic Activity ◽  
Microglial Cell ◽  
Cell Function ◽  
Microglial Cells ◽  
Phagocytosis Assay ◽  
Intracellular Ca ◽  
Β Amyloid ◽  
The Brain

AbstractThe pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses mediated by microglia. Memantine, an antagonist of N-methyl-d-aspartate (NMDA) receptors used as an anti-Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and activation of microglial cells in animal models of AD. However, it remains to be tested whether memantine can directly affect microglial cell function. In this study, we examined whether pretreatment with memantine affects intracellular NO and Ca2+ mobilization using DAF-2 and Fura-2 imaging, respectively, and tested the effects of memantine on phagocytic activity by human β-Amyloid (1–42) phagocytosis assay in rodent microglial cells. Pretreatment with memantine did not affect production of NO or intracellular Ca2+ elevation induced by TNF in rodent microglial cells. Pretreatment with memantine also did not affect the mRNA expression of pro-inflammatory (TNF, IL-1β, IL-6 and CD45) or anti-inflammatory (IL-10, TGF-β and arginase) phenotypes in rodent microglial cells. In addition, pretreatment with memantine did not affect the amount of human β-Amyloid (1–42) phagocytosed by rodent microglial cells. Moreover, we observed that pretreatment with memantine did not affect 11 major proteins, which mainly function in the phagocytosis and degradation of β-Amyloid (1–42), including TREM2, DAP12 and neprilysin in rodent microglial cells. To the best of our knowledge, this is the first report to suggest that memantine does not directly modulate intracellular NO and Ca2+ mobilization or phagocytic activity in rodent microglial cells. Considering the neuroinflammation hypothesis of AD, the results might be important to understand the effect of memantine in the brain.

scholarly journals Neuroproteomics in Epilepsy: What Do We Know so Far?

2021 ◽  
Vol 13 ◽  
Author(s):  
Amanda M. do Canto ◽  
Amanda Donatti ◽  
Jaqueline C. Geraldis ◽  
Alexandre B. Godoi ◽  
Douglas C. da Rosa ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Neural Circuit ◽  
Neurological Diseases ◽  
Epileptic Seizures ◽  
World Population ◽  
Social Burden ◽  
Neuronal Excitation ◽  
System A ◽  
Underlying Mechanisms ◽  
Patients With Epilepsy

Epilepsies are chronic neurological diseases that affect approximately 2% of the world population. In addition to being one of the most frequent neurological disorders, treatment for patients with epilepsy remains a challenge, because a proportion of patients do not respond to the antiseizure medications that are currently available. This results in a severe economic and social burden for patients, families, and the healthcare system. A characteristic common to all forms of epilepsy is the occurrence of epileptic seizures that are caused by abnormal neuronal discharges, leading to a clinical manifestation that is dependent on the affected brain region. It is generally accepted that an imbalance between neuronal excitation and inhibition generates the synchronic electrical activity leading to seizures. However, it is still unclear how a normal neural circuit becomes susceptible to the generation of seizures or how epileptogenesis is induced. Herein, we review the results of recent proteomic studies applied to investigate the underlying mechanisms leading to epilepsies and how these findings may impact research and treatment for these disorders.

Exposure of Cultured Microglial Cells to Interferon-gamma

1996 ◽  
Vol 24 (3) ◽  
pp. 377-385
Author(s):  
Inger K. Grundt ◽  
Harald Nyland
Keyword(s):  
Mhc Class Ii ◽  
Interferon Gamma ◽  
Microglial Cell ◽  
Primary Cultures ◽  
Time Lapse ◽  
Microglial Cells ◽  
Myristate Acetate ◽  
Ifn Γ ◽  
Class Ii Antigen ◽  
Mhc Class Ii Antigen

The reactions of a microglial cell population to exposure to interferon-gamma (IFN-γ) were studied in primary cultures of mixed glial cells from the brains of newborn rats. One week after seeding, the cells were exposed to 200U/ml of IFN-γ for 24 and 48 hours. After exposure to IFN-γ for 48 hours, a third of the cultures were exposed to phorbol myristate acetate (PMA) for 90 minutes. Transformation of the microglial cells in response to this treatment was observed by using a light microscope. On time-lapse film, an increase in the mobility of the cells and an increase in the number of amoeba-like microglia were among the most evident changes induced by IFN-γ. These changes became more pronounced when the exposure time was increased. The addition of PMA significantly enhanced this process. After exposure to IFN-γ for 48 hours, expression of the MHC class II antigen was observed. The interleukin-1β content of the cells was increased in the cultures after 24 hours, but declined after further exposure.

Autophagy Modulators and Neuroinflammation

2020 ◽  
Vol 27 (6) ◽  
pp. 955-982 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Jang Ho Lee ◽  
Jeiwon Cho ◽  
Guang-Ho Cha ◽  
Gyun Jee Song
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Mammalian Cells ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Scientific Interest ◽  
Therapeutic Tools ◽  
Underlying Mechanisms

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

Microbiota-Immune System Interactions in Human Neurological Disorders

2020 ◽  
Vol 19 (7) ◽  
pp. 509-526
Author(s):  
Qin Huang ◽  
Fang Yu ◽  
Di Liao ◽  
Jian Xia
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Neurological Disorders ◽  
Brain Function ◽  
Neurological Diseases ◽  
Host Immune System ◽  
Gut Dysbiosis ◽  
Characteristic Features ◽  
Novel Therapeutic Strategies

: Recent studies implicate microbiota-brain communication as an essential factor for physiology and pathophysiology in brain function and neurodevelopment. One of the pivotal mechanisms about gut to brain communication is through the regulation and interaction of gut microbiota on the host immune system. In this review, we will discuss the role of microbiota-immune systeminteractions in human neurological disorders. The characteristic features in the development of neurological diseases include gut dysbiosis, the disturbed intestinal/Blood-Brain Barrier (BBB) permeability, the activated inflammatory response, and the changed microbial metabolites. Neurological disorders contribute to gut dysbiosis and some relevant metabolites in a top-down way. In turn, the activated immune system induced by the change of gut microbiota may deteriorate the development of neurological diseases through the disturbed gut/BBB barrier in a down-top way. Understanding the characterization and identification of microbiome-immune- brain signaling pathways will help us to yield novel therapeutic strategies by targeting the gut microbiome in neurological disease.

scholarly journals Neuronutraceuticals Modulate Lipopolysaccharide- or Amyloid-β 1-42 Peptide-Induced Transglutaminase 2 Overexpression as a Marker of Neuroinflammation in Mouse Microglial Cells

2021 ◽  
Vol 11 (12) ◽  
pp. 5718
Author(s):  
Nicola Gaetano Gatta ◽  
Andrea Parente ◽  
Francesca Guida ◽  
Sabatino Maione ◽  
Vittorio Gentile
Keyword(s):  
Microglial Cell ◽  
Amyloid Β ◽  
Transglutaminase 2 ◽  
Microglial Cells ◽  
Tissue Type ◽  
Microglial Cell Line ◽  
Bv2 Cells ◽  
Important Marker

Background: Tissue type 2 transglutaminase (TG2, E.C. 2.3.2,13) is reported to be involved in the phagocytosis of apoptotic cells in mouse microglial BV2 cells and peripheral macrophages. In this study, by using lipopolysaccharide (LPS)- or amyloid-β 1-42 (Aβ 1-42) peptide-stimulated microglial cell line BV2 and mouse primary microglial cells, we examined the effects of different neuronutraceutical compounds, such as curcumin (Cu) and N-Palmitoylethanolamine (PEA), known for their anti-inflammatory activity, on TG2 and several inflammatory or neuroprotective biomarker expressions. Methods: Mouse BV2 cells were treated with LPS or Aβ1-42 in the presence of curcumin or PEA, in order to evaluate the expression of TG2 and other inflammatory or neuroprotective markers using Real Time-PCR and Western blot analyses. Results: Curcumin and PEA were capable of reducing TG2 expression in mouse microglial cells during co-treatment with LPS or Aβ 1-42. Conclusions: The results show the role of TG2 as an important marker of neuroinflammation and suggest a possible use of curcumin and PEA in order to reduce LPS- or Aβ1-42-induced TG2 overexpression in mouse microglial cells.

Trend of Hospital Admission and Outcome Study of Patients Admitted in a Neurology Unit at a Tertiary Care Neuroscience Hospital in Bangladesh

2018 ◽  
Vol 4 (2) ◽  
pp. 69-74
Author(s):  
Md Tauhidul Islam Chowdhury ◽  
Mohammad Shah Jahirul Hoque Choudhury ◽  
KM Ahasan Ahmed ◽  
Mohammad Sadekur Rahman Sarkar ◽  
Md Abdullah Yusuf ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
Tertiary Care ◽  
Length Of Hospital Stay ◽  
Retrospective Chart Review ◽  
Total Death ◽  
Neurological Patients ◽  
Study Population ◽  
The Mean ◽  
Day By Day

Background: Neurological disorders is becoming a growing concern both for developed and developing countries. Magnitude of the problem is increasing day by day. Among all neurological disorders, stroke is the leading cause of morbidity and mortality globally.Objectives: The purpose of the study was to see the trend of admission of patients with neurological diseases and to study the outcome of patients at referral neurology hospital in Bangladesh.Methodology: This retrospective chart review was conducted in the blue unit of the Department of Neurology at National Institute of Neurosciences and Hospital, Dhaka, Bangladesh from 1st January to 31st December 2016 for a period of one (01) year. All the admitted patients with both sexes were selected as study population. The outcome was observed among the study population.Result: A total number of 1044 patients were admitted during the study period. Majority of the patients were in the age group of the 41 to 50 years which was 417(39.9%) cases. Both male and female were in highest number in the month of May which was 63 and 48 cases respectively. The total death of the study population was 146(14.0%) cases. The mean length of hospital stay was 8.4±2.31 days.Conclusion: Middle aged male is the main bulk of the neurological patients, admitted in a referral neurology hospital in Bangladesh. Highest admission and mortality was observed in stroke patients.Journal of National Institute of Neurosciences Bangladesh, 2018;4(2): 69-74

scholarly journals Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

2020 ◽  
Vol 21 (10) ◽  
pp. 3483 ◽  
Author(s):  
Przemysław Koźmiński ◽  
Paweł Krzysztof Halik ◽  
Raphael Chesori ◽  
Ewa Gniazdowska
Keyword(s):  
Folic Acid ◽  
Combination Therapy ◽  
Autoimmune Diseases ◽  
Myasthenia Gravis ◽  
Neurological Disorders ◽  
Chemotherapeutic Agent ◽  
Neurological Diseases ◽  
Immunosuppressive Drug ◽  
Structural Analogue ◽  
Potential Benefits

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer’s disease or myasthenia gravis will be discussed.

First person – Fanny Jaudon and Martina Albini

2021 ◽  
Vol 134 (16) ◽  
Keyword(s):  
Neurotrophic Factor ◽  
Neurological Disorders ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Early Career ◽  
First Person ◽  
Early Career Researchers ◽  
And Function ◽  
The University ◽  
Selection Of

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Fanny Jaudon and Martina Albini are co-first authors on ‘ A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor’, published in JCS. Fanny is a postdoc at the University of Trieste in the lab of Lorenzo A. Cingolani at Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova, Italy, investigating the molecular mechanisms controlling development and function of neuronal circuits and implementing genome-editing approaches for the treatment of neurological disorders. Martina is a PhD student at the Istituto Italiano di Tecnologia in the lab of Fabio Benfenati and Fabrizia Cesca investigating neurotrophin biology and its involvement in neurological diseases.

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