Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Microglia”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed1996

Receptor-mediated phagocytosis of myelin by macrophages and microglia: effect of opsonization and receptor blocking agents.

Myelin is phagocytosed by microglia (MG) and to a somewhat lesser extent by peritoneal macrophages (M phi) in a dose- and time-dependent manner. In serum-free medium opsonization of rat myelin significantly enhances binding and ingestion, more by rat macrophages than by microglia. Furthermore the requirement for opsonization is not restricted to anti-myelin antibodies as the difference in the rate of myelin uptake by macrophages is largely eliminated when they are cultured in 10% fetal calf serum. Binding and ingestion of both myelin and opsonized myelin are inhibited to the same dose-dependent extent by zymosan, oxidized LDL, peroxidase-antiperoxidase (PAP), opsonized erythrocytes and the anti-CR3 antibody OX42 implicating lectin, scavenger, Fc and complement receptors in the phagocytosis of myelin. Thus while the differential uptake of myelin and opsonized myelin by macrophages would indicate a central role for the Fc receptor, binding inhibition studies implicate a range of membrane receptors which would obviate the need for antigen-antibody complexing to stimulate phagocytosis. Uptake of both myelin preparations by macrophages or microglia is stimulated by interferon-gamma and inhibited by TGF-beta, and the process of ingestion results in increased nitric oxide release and decreased superoxide production, the effect being more pronounced when myelin is opsonized.

Animals↗
PubMedDate not supplied

Alzheimer's disease cerebrospinal fluid antibodies display selectivity for microglia. Investigations with cell cultures and human cortical biopsies.

Previous investigations demonstrated that the cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients contains antibodies that recognize specific neuronal populations in the adult rat central nervous system (CNS). These findings suggest a pathogenic role for immunological aberrations in this disorder. To determine if antibodies may provide a means to differentially diagnose the dementias, CSF from a diversified dementia population was screened against the developing rat CNS and a cell culture system. Markings produced by AD CSF were distinctly different from those of vascular dementias (VAD) against the developing rat CNS. More importantly, some AD CSF recognized amoeboid microglia. The recognition of amoeboid microglia by antibodies in AD CSF is particularly interesting since these cells proliferate in response to nervous system disease and also engulf debris. A cell culture technique was developed to allow the rapid screening of CSF antibodies. Patient CSF produced five different types of markings in the cell culture: microglia, glioblasts, fibers, nonspecific, or negative. Correlations with these structures and the diagnosis of four different dementia populations revealed that, in comparison to the other groups, AD CSF displayed remarkable selectivity toward microglial cells. Cortical biopsies from patients suspected to have AD were incubated with the patient's own CSF and that of confirmed AD patients. Both CSF samples recognized microglial cells in the patient's cortical biopsy. The same CSF samples incubated against normal human cortical autopsy or a biopsy from a 3-mo-old child displayed negative immunoreactivity. These three approaches suggest that the presence of CSF microglial antibodies may be a means to distinguish AD patients from other dementias. The results add further support to the widely growing concept that inflammation and similar immune mechanisms may contribute to AD pathogenesis.

Alzheimer Disease↗
PubMed2003

Ursodeoxycholic acid inhibits pro-inflammatory repertoires, IL-1 beta and nitric oxide in rat microglia.

Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production. In the present study, we hypothesized that UDCA may inhibit the production of the pro-inflammatory cytokine, IL-1beta, and nitric oxide (NO) in microglia. In the study, we found that 100 microg/mL UDCA effectively inhibited these two pro-inflammatory factors at 24 h and 48 h, compared to the Abeta42-pretreated groups. These results were compared with the LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by several stimulants, such as Abeta42, in Alzheimers brain and can release those inflammatory factors, the ability to inhibit or at least decrease the production of IL-1beta and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA and the Griess Reagent System, we therefore found that UDCA in Abeta42 pre-treated cultures played a significant role in suppressing the expression or the production of IL-1beta and NO. Similarly, lipopolysaccharide (LPS) did not activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may play an important role in chronic cell damage due to this long effect. These results further imply that UDCA could be an important cue in suppressing the microglial activation stimulated by massive Aâ peptides in the AD progressing brain.

Animals↗
PubMed1997

Activation of microglia in the brains of humans with heart disease and hypercholesterolemic rabbits.

Activated microglial cells are concentrated in senile plaques characteristic of Alzheimer's disease. Such accumulations of activated microglia may contribute towards neurodegeneration via production of cytokines and free radicals. Studies suggesting a link between Alzheimer's disease and heart disease led us to study microglia immunohistochemically, using monoclonal antibody LN-3, in age-matched nondemented humans with and without heart disease. Using a qualitative staging system for assessing morphological changes occurring in microglia, we found higher microglial activation in the brains of subjects with heart disease than in those without it. Lectin histochemical examination of brains from rabbits maintained on a high-cholesterol diet also revealed increased microglial activation and leukocyte infiltration. Collectively our observations from humans and rabbits suggest that hypercholesterolemia and heart disease accelerate brain aging, and that the formation of senile plaques may be the end result of progressive microglial activation that occurs with aging.

Aged↗
PubMed2006

Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization.

Immunological alterations have been demonstrated in peripheral blood and cerebrospinal fluid of patients with schizophrenia, while previous postmortem studies have provided an inconsistent picture as to the role of microglia in the context of schizophrenia. Microglial activation is a sensitive indicator of changes in the CNS microenvironment, such as inflammatory and neurodegenerative processes. The aim of the present postmortem study was to examine HLA class II (HLA-DR) expression on microglia in brain regions which are particularly relevant for schizophrenia, with regard to hemispheric lateralization. Dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), hippocampus and mediodorsal thalamus (MD) were studied in 16 cases with schizophrenia and 16 control subjects. Immunostaining was found in all brain regions and was not restricted to macrophage-like ameboid cells, but also appeared in ramified cells. Region-specific HLA-DR-positive cell density was not significantly different between cases with schizophrenia and controls. However, ameboid microglial cells were lateralized towards the right hemisphere in healthy subjects but not in the schizophrenia group (P=0.01). Postmortem interval correlated with ramified cell numbers in ACC/DLPFC (P=0.01/0.04) and ameboid cell density in hippocampus (P=0.03). Age, gender, duration of disease, medication dosage, storage delay and whole brain volume had no effect. Single case analysis revealed highly elevated microglial cell numbers in ACC and MD of two schizophrenic patients who had committed suicide during acute psychosis. In conclusion, the present data suggest the absence of microgliosis but decreased cerebral lateralization of ameboid microglia in schizophrenia.

Adult↗
PubMed1999

Reactive microglia in aging and dementia: an immunohistochemical study of postmortem human brain tissue.

Significantly increased up-regulation of HLA DR (major histocompatibility complex class II antigen) was seen using immunohistochemistry in postmortem brain tissue from demented patients with Alzheimer's disease (AD) (73 cases, 61 females/12 males, mean age 84 +/- 9 years) compared to controls (22 cases, 10 females/12 males, mean age 78 +/- 9 years). The counts of HLA DR-expressing activated microglia were significantly higher in female AD patients compared to males, significantly higher in AD patients with the age at death greater than 75 years compared to those dying younger and higher, although not statistically significantly, in AD patients with the apolipoprotein E (ApoE) epsilon4 allele compared to those patients not carrying this allele. In contrast to the situation in AD patients, in the control cases the HLA DR expression was higher in males compared to females. Furthermore, in the very old non-demented patients (age at death > 80 years), a decrease in the up-regulation of HLA DR expression was observed. A significant correlation between activated microglia and neurofibrillary tangles was seen in female AD patients compared to males, in AD cases without ApoE epsilon4 allele compared to those with this allele, in sporadic cases compared to familial and in cases with senile rather than presenile onset of the disease. Our results indicate that there is an age- and/or sex-related variability in up-regulation of HLA DR expression of microglia and that the linkage between this up-regulation and AD lesions is significantly influenced by the ApoE epsilon4 allele, gender of subjects, age at onset and familiality of the disease.

Age Factors↗
PubMed2006

Purinergic signaling and microglia.

Microglial cells are considered as the pathologic sensors of the brain. In this paper, we review mechanisms of purinergic signaling in microglia. As ATP is not only considered as a physiological signaling substance but is also elevated in pathology, it is not surprising that microglia express a variety of P2X, P2Y and adenosin receptors. As a rapid physiological event, ATP triggers a cationic conductance, increases the potassium conductance and also elicits a calcium response. As a long-term effect, purinergic receptor activation is linked to the movement of microglial processes and, in the context of pathology, to chemotaxis. The purinoreceptors also modulate the release of substances from microglia, such as cytokines, nitric oxide, or superoxide, which are important in the context of a pathologic response.

Adenosine Triphosphate↗
PubMed2002

Amyloid cored plaques in Tg2576 transgenic mice are characterized by giant plaques, slightly activated microglia, and the lack of paired helical filament-typed, dystrophic neurites.

We examined the brains of Tg2576 transgenic mice carrying human amyloid precursor protein with the Swedish mutation and Alzheimer's disease (AD) by means of immunohistochemistry and electron microscopy to clarify the characteristics of amyloid-associated pathology in the transgenic mice. In 12- to 29-month-old Tg2576 mice, congophilic cored plaques in the neocortex and hippocampus were labeled by all of the Abeta1-, Abeta40- and 42-specific antibodies, as seen in the classical plaques in AD. However, large-sized (>50 micro m in core diameter) plaques were seen more frequently in the older mice (18-29 months) than in those with AD (approximately 20% vs 2% in total cored plaques), and Tg2576 mice contained giant plaques (>75 micro m in core diameter), which were almost never seen in the brain of those with AD. Neither thread-like structures nor peripheral coronas were observed in the cored plaques of the transgenic mice in the silver impregnations. Immunohistochemically, plaque-accompanied microglia showed a slight enlargement of the cytoplasm with consistent labeling of Mac-1 and macrosialin (murine CD68), and with partial labeling of Ia antigen and macrophage-colony stimulating factor receptor. Ultrastructurally, the microglia surrounding the extracellular amyloid fibrils in the large, cored plaques showed some organella with phagocytic activity, such as secondary lysosomal, dense bodies, but intracellular amyloid fibrils were not evident. Dystrophic neurites in the plaques of the transgenic mice contained many dense multilaminar bodies, but no paired helical filaments. Our results suggest that giant cored plaques without coronas or paired helical filament-typed, dystrophic neurites are characteristic in Tg2576 mice, and that plaque-associated microglia in transgenic mice are activated to be in phagocytic function but not sufficient enough to digest extracellularly deposited amyloid fibrils.

Alzheimer Disease↗
PubMed2003

GDNF and TGF-beta1 promote cell survival in serum-free cultures of primary rat microglia.

Recent evidence indicates that glial cell line-derived neurotrophic factor (GDNF) may influence microglial survival, proliferation, and activation, but this has not yet been tested on isolated primary microglia. We compared the effects of individual and combined application of 10 ng/ml GDNF and 1 ng/ml transforming growth factor-beta1 (TGF-beta1) on total cell number, 5-bromo-2'-deoxyuridine (BrdU) incorporation, DNA nick-end labelling (TUNEL staining), and nitrite and lactate dehydrogenase (LDH) secretion in serum-free cultures of primary rat microglia. GDNF as well as TGF-beta1 enhanced the total number of lectin-positive cells and decreased the number of TUNEL-positive nuclei, while no effect on proliferation was observed. Both factors suppressed the secretion of nitrite during the first 4 days of culturing, and GDNF but not TGF-beta1 reduced the secretion of LDH in 2-week-old cultures. These findings suggest that GDNF and TGF-beta1 support survival of primary microglia in vitro.

Animals↗
PubMed1997

Ramification of microglia, monocytes and macrophages in vitro: influences of various epithelial and mesenchymal cells and their conditioned media.

Microglial cells are able to switch between an "active" amoeboid and a ramified "resting" morphology during development and after experiencing lesions. We have previously shown that in vitro microglial morphology is controlled by their cellular environment, i. e. cells become ramified in astrocyte coculture but amoeboid on monolayers of fibroblasts. In the present study we have extended the analysis of the control of macrophage morphology by maintaining macrophages of different origins in coculture with different epithelial or mesenchymal cells and their conditioned media. Microglia, monocytes and spleen macrophages seeded onto monolayers of astrocytes, kidney epithelia or hepatoma cells developed the ramified morphology but remained amoeboid in fibroblast coculture. Ramification was also induced by media conditioned by these cells as well as by phorbolic esters, i.e. activators of protein kinase C. In double coculture assays, even small numbers of fibroblasts were able to override the "epithelial" influence. Likewise, microglia remained amoeboid, when incubated on several constituents of the extracellular matrix. These results indicate that macrophage ramification is an active process initiated by diffusible factors secreted by various epithelial cells, possibly acting upon a protein-kinase-C-related receptor. We interprete the modification of macrophage morphology as a functional adaptation to the surrounding type of tissue that is enforced by its constituent cells. Thus, the specific morphologies of microglia, hepatic von Kupffer's cells or peritubular kidney macrophages could be explained by similar epithelium-macrophage interaction.

Animals↗
PubMed1997

Rabies viruses infect primary cultures of murine, feline, and human microglia and astrocytes.

Recent studies have reported the detection of rabies viral antigens and virions in astrocytes and microglia of rabies-infected animals. As a first step toward understanding whether these glial cells may be involved in rabies virus replication, persistence, and/or pathogenesis, we explored their potential to be infected in vitro. Primary cultures of murine, feline, and human microglia and astrocytes were infected with several different rabies viruses: two unpassaged street virus isolates, a cell culture-adapted strain, and a mouse brain-passaged strain. Infection, as determined by immunofluorescence, was detected in 15 of the 16 (94%) virus-glial cell combinations. Replication of infectious virus, determined by infectivity assay, was detected in 7 of the 8 (88%) virus-cell combinations. These results show that astrocytes and microglia can be infected by rabies viruses, suggesting that they may have a potential role in disease, perhaps contributing to viral spread, persistence and/or neuronal dysfunction.

Animals↗
PubMed2005

Role of microglia in multiple sclerosis.

Microglia are the resident macrophages of the nervous system. They serve to protect and preserve neuronal cells from pathogens and facilitate recovery from metabolic insults. In addition, they appear to play a role in the neuropathology of noninfectious inflammatory disorders of the central nervous system, especially those that are autoimmune. Presentation of neural autoantigens to autoreactive T cells by microglia and the attendant secretion of proinflammatory cytokines are thought to facilitate the inflammatory process in diseases such as multiple sclerosis. They also serve as scavengers of damaged myelin following death of oligodendrocytes and the destruction of myelin and may, therefore, promote recovery of myelin damaged by the inflammatory insult. This review examines the current controversies on the pathology of multiple sclerosis and the role played by microglia in the development of central nervous system demyelination.

Animals↗
PubMed1995

Occurrence of the opiate alkaloid-selective mu3 receptor in mammalian microglia, astrocytes and Kupffer cells.

Evidence is presented for occurrence of opiate alkaloid-selective, opioid-peptide-insensitive receptor binding sites, labeled with [3H]morphine, in primary cultures of cat microglia and cat astrocytes, as well as on highly purified preparations of rat Kupffer cells. These receptors have been designated mu3 on the basis of their close similarity to receptors first found to be present on human peripheral blood monocytes. Exposure of the microglia to morphine and etorphine caused marked quantifiable changes in cellular morphology, including assumption of a more rounded shape and retraction of cytoplasmic processes; in contrast, several opioid peptides were without effect on morphology. The effects of morphine on microglial morphology were blocked by the opiate antagonist naloxone. These effects of drugs on morphology were as predicted for action via the mu3 receptor. Opiate alkaloid binding sites previously detected on the rat C6 glioma cell line were also characterized here as of the mu3 receptor subtype. It is proposed that mu3 receptors have broad distribution in different macrophage cell types of bone marrow lineage, including microglia and Kupffer cells. Furthermore, these receptors are not restricted to cells of bone marrow lineage, since they are also present on astrocytes.

Alkaloids↗
PubMed1995

Cation and anion unitary ion channel currents in cultured bovine microglia.

The use of excised patches has led to the identification and characterization of two channels not previously reported in microglia. A calcium-dependent K+ channel K(Ca) was activated in inside-out patches obtained from cultured bovine microglia and had a unitary conductance of 240 pS with symmetrical 140 mM K+ across patches. Mean open times of K(Ca) were exponentially dependent on patch potential and were increased with patch depolarization. Channel open probability (Popen) was increased with patch depolarization with either 5 mM or 140 mM internal K+ and was attributable to potential dependent enhancement of both opening frequency and mean open time. Whole cell currents showed the presence of a slowly activating K+ conductance, blocked by external TEA (at 2 mM) and likely the macroscopic correlate of the unitary K(Ca); half-maximal activation of the current occurred at +25 mV. An anion channel (unitary conductance of 325 pS with symmetrical Cl- across patches) was activated in inside-out patches with depolarizing and hyperpolarizing potential steps from 0 mV. Channel activation was not dependent on internal Ca2+. The anion currents inactivated during maintained potential steps with the time constant for inactivation faster with increased patch depolarization. The properties of the K(Ca) and anion channels in microglia membrane may have relevance to cell function in response to neuronal damage in the CNS.

Animals↗
PubMed1995

Graded expression of immunomolecules on activated microglia in the hippocampus following ischemia in a rat model of ischemic tolerance.

Preconditioning of the brain with sublethal ischemia protects against neuronal damage following subsequent longer periods of ischemia (ischemic tolerance). In order to evaluate the potential involvement of microglial activation in ischemic tolerance, we immunohistochemically visualized microglial cells in the hippocampus in a rat model of ischemic tolerance. Three minutes of forebrain ischemia (preconditioning ischemia) or sham operation was followed by 6 min of ischemia (second ischemia) 3 days later. The brains were perfusion-fixed after 2 h, 1 day, 3 days, and 7 days. Microglial cells were localized by histochemical staining with isolectin-B4 from Griffonia simplicifolia and by immunohistochemistry of immunomolecules with monoclonal antibodies against major histocompatibility complex class I (OX18) and class II (OX6) antigens and complement receptor type 3 (OX42) and with a rat macrophage marker ED1 and a pan-T cell marker W3/13. Quiescent microglia were stained only by OX42. Preconditioning ischemia led to moderate microglial activation as shown by staining with isolectin, OX42, and OX18. Six minutes of ischemia (without preconditioning) caused early generalized microglial activation as shown by lectin and OX42 after 2 h and by OX18 after 1 day. This length of ischemia produced CA1 neuronal destruction after 3 and 7 days when we observed phagocytic transformation of microglia and increased expression of immunomolecules including OX6 and ED1 However, no staining was seen with W3/13. Following 6-min ischemia with preconditioning, early microglial activation was observed with lectin, OX42, and OX18, but CA1 neuronal damage was prevented and the microglial activation returned toward normal after 7 days. Thus, activation of microglia and expression of immunomolecules occurred in a graded and controlled fashion in response to different degrees of neuronal injury.

Adaptation, Physiological↗
PubMed1994

Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of IgG.

Receptors for the Fc part of IgG, FcRI (CD64), FcRII (CD32), and FcRIII (CD16) were studied by indirect immunoperoxidase staining of cryostat sections from normal and multiple sclerosis (MS) brains. Microglia in the parenchyma of normal white matter had a dendritic morphology, and were weakly stained by monoclonal antibodies (mAbs) to FcRI, FcRII, and FcRIII. In active MS lesions reactive microglia were strongly stained by the mAbs 32.2 (FcRI), IV-3 (FcRII), and 3G8 (FcRIII). Perivascular macrophages were stained by all anti-FcR mAbs in both normal white matter and in MS lesions, whereas endothelial cells were stained by the anti-FcRIII mAb only. The FcR on microglia and perivascular macrophages may be of functional importance in antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, and local immunoregulation. FcR on endothelium may be of importance in binding and transportation of immune complexes into the CNS. FcR mediated functions may consequently be highly relevant to the pathogenesis of MS.

Adult↗
PubMed1994

Induction of MHC class II antigen expression on murine microglia by interleukin-3.

The effects of various cytokines on MHC class II antigen expression were examined in murine microglia. Interleukin-3 (IL-3), as well as interferon-gamma (IFN-gamma), induced MHC class II antigen expression on these cells. IL-3 additionally enhanced MHC class II antigen expression induced by IFN-gamma. The induction of MHC class II antigen expression by IL-3 was not mediated via IFN-gamma production, because the effect was not blocked by antibodies to IFN-gamma. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF) did not affect the expression of MHC class II antigen on naive cells and down-regulated IFN-gamma-mediated induction of MHC class II antigen expression on microglia. Because IL-3 and GM-CSF are apparently produced in the central nervous system, MHC class II antigen expression on microglia may be regulated by these cytokines synthesized in the central nervous system.

Animals↗
PubMed1994

Expression of MRP14, 27E10, interferon-alpha and leukocyte common antigen by reactive microglia in postmortem human brain tissue.

We have immunohistochemically investigated the localization of a panel of leukocyte-related molecules in postmortem human brain tissue from control subjects and patients with Alzheimer's disease (AD). Microglia constitutively express leukocyte common antigens (LCA) with CD45RB determinants. Depending on the state of activation, microglia become positive for the myeloid cell-specific calcium binding protein MRP14, LCA with CD45RO determinant, interferon-alpha, and an antigen recognized by monoclonal antibody 27E10. In AD lesions, these cells are activated in a manner consistent with a chronic inflammatory state. The results of this study have shown further parallels in protein expression between activated microglia and activated leukocytes of the myeloid lineage.

Aged↗