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PubMed1993

Resident macrophages (ramified microglia) of the adult brown Norway rat central nervous system are constitutively major histocompatibility complex class II positive.

A flow cytometric phenotype for isolated adult central nervous system (CNS) ramified microglia was previously defined (CD45low CD11b/c+) in the Lewis strain rat, that clearly distinguished these cells from all blood-derived leucocytes, the latter being CD45high. Consistent with the reported lack of major histocompatibility complex (MHC) expression in the CNS, isolated microglia were mostly MHC class II-. Employing these phenotypic criteria, we now show that a proportion of microglia in Brown Norway (BN) strain rats are constitutively MHC class II+. In spinal cord, up to 25% of microglia are distinctly positive and most have some level of expression. In situ staining of MHC class II+ microglial cells in BN rats indicates that positive cells are typical of ramified microglia on the grounds of both morphological appearance and anatomical location. In Lewis (LEW) rats, the few MHC class II-expressing cells isolated from the normal CNS are CD45high blood-derived cells and not resident microglia. After infection of both LEW and BN rats with a neurotropic murine hepatitis virus (MHV-JHM), MHC class II was rapidly upregulated on microglia in the BN but not in the LEW strain. In the latter, inflammatory cells were the predominant MHC class II-expressing population. Nevertheless, most microglia in the LEW strain could, after some delay, be induced to express MHC class II after transfer of an experimental autoimmune encephalomyelitis (EAE)-inducing encephalitogenic T cell line. Paradoxically, strains resistant to EAE (exemplified by the BN) contained more constitutive MHC class II-expressing microglia than susceptible ones, when a variety of strains were examined. The results clearly establish that the normal CNS may contain MHC class II-expressing cells that are a resident rather than a transient blood-derived population. It is significant that this expression is strain related, but there is no evidence that microglial cell constitutive MHC class II expression predisposes to EAE susceptibility.

Animals↗

PubMed1996

Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia.

Microglial cells are resident cells of the CNS and are implicated as regulators and effectors of immune responses which occur within this compartment. The precise role of parenchymal microglia remains speculative because distinctions between these cells, perivascular "microglia," and blood-derived monocytes/macrophages are not well defined. The current study describes the phenotype and function of microglia immediately upon isolation from the non-inflamed adult human CNS and the phenotypic changes which occur in these cells when maintained in tissue culture. We find that the characteristic phenotype of immediately ex vivo parenchymal microglia (CD11c+/CD45low/CD14) corresponds to that found in situ in the "normal" human brain. The phenotype differs from that of perivascular "microglia" in situ and PBDM (both CD45hi/CD14++). The immediately ex vivo microglia express B7-2 and HLA class II molecules and can support alloantigen-induced proliferation by CD4+ T cells freshly isolated from peripheral blood. Following in vitro culture, the cells are characterized by a bipolar morphology, continued lower levels of CD45 expression compared to PBDM, and slight upregulation of B7-1 and HLA-DR antigen expression. CD14 becomes expressed at high levels on the cells, suggesting that CD14 can serve as an apparent marker of microglia activation which is not based on changes in morphology or APC capacity. Further, treatment of the cells with IFN-gamma and LPS causes further upregulation of HLA-DR and clear expression of B7-1 molecules on the surface. The capacity to characterize phenotypic and functional properties of microglia before and after activation provides an opportunity to determine means to manipulate the immune regulatory and effector properties of this cell type.

Adult↗

PubMed1996

The transition of microglia to a ramified phenotype is associated with the formation of stable acetylated and detyrosinated microtubules.

In situ and in vitro, microglia can have different morphologies, which are thought to reflect distinct physiological activities. Two extreme forms are ameboid and ramified microglia. To study cytoskeletal changes during differentiation, we used defined cell culture systems to yield cultures of ameboid or ramified microglia from mouse brain. With respect to proliferation, secretion, receptor-expression, and phagocytosis, ramified microglia was generally less active. We found that the transition to a ramified phenotype was accompanied by an increase in the relative amount of acetylated and detyrosinated tubulin. Whereas the modified microtubules were restricted to regions close to the microtubule-organizing centers (MTOCs) in ameboid cells, acetylated microtubules were abundant in ramified cells, where they appeared to traverse from one process to another with no apparent anchoring at MTOCs. The increase in acetylated and detyrosinated microtubules was paralleled by an increased stability against nocodazole-induced microtubule disassembly and by a lower rate of change in the length of the processes. Staining of retinal wholemounts confirmed the presence of acetylated microtubules in ramified microglia in situ. We conclude that during the transition of microglia to a ramified phenotype regulated processes exist, which cause a reorganization of microtubules and a change in composition of the microtubule skeleton resulting in a less dynamic and more stable microtubule network. Intracellular factors that are specifically involved in microtubule stabilization in ramified microglia need to be identified in future research and may provide a useful criterion for defining ramified microglia.

Acetylation↗

PubMed2003

Microglia density decreases with age in a mouse model of Huntington's disease.

Huntington's disease (HD) is characterized by selective neuronal loss and reactive gliosis. In the R6/2 transgenic HD mouse model, there is no selective cell loss, although astrocytosis has been reported. Since there have been no previous studies on microglia in this model, we have undertaken a detailed investigation of microglia in six different forebrain regions in the R6/2 mouse and their wild-type littermates at two time points. Microglia were identified using the histochemical marker isolectin B4 and interactions of genotype, region, and age were analyzed. Results showed that there was a significant decrease in the number of microglia with age in both wild-type and R6/2 brains, which was more pronounced in the transgenic mouse. There were also morphological changes with age observed in both genotypes. As early as 7 weeks of age, structural microglial abnormalities could be seen in R6/2 brains, including bulbous swellings and long stringy processes; comparable changes were seen at 16 weeks in wild-type brains. At 14.5 weeks, microglia in R6/2 mouse brains were smaller in size with condensed nuclei and fragmentation of their processes. We suggest that the density and morphology of microglia change with normal aging and that this process is accelerated in R6/2 brains. Such changes in the dynamic status of microglia may lead to an impairment of their neurosupportive functions. Further studies are needed to understand better the role of microglia in aging and neurodegeneration.

Aging↗

PubMed2004

Progressive telomere shortening occurs in cultured rat microglia, but not astrocytes.

Normal somatic cells have a finite replicative capacity. With each cell division, telomeres shorten progressively until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell types in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. In this study, we show that telomere shortening accompanied by low to moderate telomerase activity, and ultimately senescence, occurs in rat microglia in vitro. When microglia are stimulated to divide with the mitogen granulocyte macrophage-colony stimulating factor (GM-CSF), longer telomeres are allowed to shorten, while shorter telomeres are lengthened. Telomerase activity is nearly 3-fold higher in GM-CSF-stimulated microglia initially, relative to unstimulated controls, and then declines to levels below those seen in controls before increasing again. Telomere attrition is also more rapid when microglia are grown in culture dishes of increasing size. Fluorescence in situ hybridization (FISH) analysis indicates that a nearly 3-fold variation in both inter- and intra-chromosomal telomere length exists in microglia. In contrast to microglia, cultured astrocytes exhibit a cyclical pattern of telomere lengthening and shortening over time, corresponding to a similar cycle of higher and lower telomerase activity. When astrocytes are passaged, mean telomere length increases initially from passage 1-2, remaining constant until passage 5, while the shortest telomeres are continually lengthened. In conclusion, the telomere shortening evident in microglia is accompanied by their progression to senescence by 32 days in vitro. In contrast, astrocytes, perhaps due to greater telomerase activity, have longer life spans and may be passaged repeatedly before entering senescence. Our findings provide an impetus to investigate the possibility that microglial telomere shortening may occur in vivo.

Animals↗

PubMed2005

Toll-like receptor 2 (TLR2) is pivotal for recognition of S. aureus peptidoglycan but not intact bacteria by microglia.

Toll-like receptor 2 (TLR2) is a pattern recognition receptor that plays an important role in enabling cells of the innate immune system to recognize conserved structural motifs on a wide array of pathogens including gram-positive bacteria. Although microglia have recently been shown to express TLR2, the functional significance of this receptor in mediating microglial activation remains unknown. To ascertain the importance of TLR2 in microglial responses to S. aureus and its cell wall product peptidoglycan (PGN), we evaluated primary microglia from TLR2 knockout (KO) and wild-type (WT) mice. TLR2 was found to play a pivotal role in PGN recognition and subsequent activation in primary microglia, as demonstrated by the attenuated expression of TNF-alpha, IL-12 p40, MIP-2, and MCP-1 in PGN-treated TLR2 KO microglia compared with WT cells. In contrast, the responses of TLR2 KO and WT microglia to S. aureus were qualitatively similar, indicating that alternative receptors are responsible for recognizing intact bacteria. Microarray analysis confirmed that TLR2 plays a central role in PGN recognition by primary microglia. The expression of MyD88, a central adapter molecule in TLR-dependent signaling, was similar in both TLR2 KO and WT microglia, suggesting that the defect in PGN recognition by the former is not due to alterations in this key signaling intermediate. These findings reveal the complex nature of gram-positive bacterial recognition by microglia, which occurs, in part, through engagement of TLR2.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Origin of microglia.

This paper reviews the various proposed hypotheses on the origin of microglia. The seminal study of del Rio-Hortega first stated that the cells were derived from the mesodermal pial cells that invaded the brain during embryonic development. Along with this was the description of precursor cells in the yolk sac in early development. Our results in the embryonic mouse brain have shown the occurrence of lectin-labelled precursor cells at the yolk sac that later appeared in the mesenchymal tissue associated with the neuroepithelium where they penetrated the nervous tissue to become the microglia. A second major view has held that microglia are of neuroectodermal origin; the cells either originate from glioblasts or the germinal matrix. Another school of thought is that microglia are derived from blood monocytes. In this connection, circulating monocytes enter the developing brain to assume the form as amoeboid microglia that subsequently evolve to become the ramified microglia. In traumatic brain lesions following an intravenous injection of colloidal carbon as a cytoplasmic marker for monocytes, it was found that carbon-labelled monocytes were the main source of brain macrophages, some of which transformed into microglia during the healing process. In conclusion, our results derived from the normal and altered brain development as well as from experimental lesions tend to favour the view of the monocytic nature of microglia. Recent studies by us also point to the possibility that some microglial cells may arise from the pial mesenchymal macrophages that appear to originate from the yolk sac precursors.

Animals↗

PubMed2005

Neuroprotective role of microglia expressing interleukin-4.

Little is known about the underlying mechanisms responsible for the death of activated microglia and the functional consequences of the death of these cells, especially in vivo. We show here that intracortical injection of lipopolysaccharide (LPS) led to upregulation of interleukin-4 (IL-4) immunoreactivity, followed by a substantial loss of microglia 3 days later, as visualized by complement receptor type 3 (OX-42) immunostaining and tomato lectin staining. Cells positive for caspase-3 and terminal deoxynucleotidyl transferase mediated fluorescein-dUTP nick-end labeling (TUNEL) were also localized within LPS-activated microglia. IL-4 immunoreactivity was detected as early as 12 hr post-LPS, disappearing at 72 hr. Surprisingly, IL-4 immunoreactivity was detected exclusively in microglia, but not in astrocytes or neurons. In addition, IL-4-neutralizing antibodies markedly increased the survival of activated microglia at 3 days post-LPS. The expression of inducible nitric oxide synthase (iNOS) and tumor-necrosis factor (TNF)-alpha was sustained in parallel in activated microglia, consequently increasing neuronal cell death. To our knowledge, this study is the first to show the endogenous expression of IL-4 in LPS-activated microglia in vivo. Our findings suggest that IL-4 may regulate brain inflammation by inducing the death of activated microglia in vivo and increasing neuronal survival.

Analysis of Variance↗

PubMed1994

Activation of adult human derived microglia by myelin phagocytosis in vitro.

The present study was designed to determine the extent to which cultured glial cells phagocytose normal central nervous system (CNS) myelin and CNS myelin opsonized with serum or purified antibody against myelin basic protein (MBP). Glial cells studied were mixed cultures (consisting of astrocytes, microglia, and oligodendrocytes) and enriched microglia established from adult human brain specimens and enriched astrocytes from fetal human brain. A human monocytic cell line, THP-1, was included as a control. Uptake of 125I-labelled myelin was followed over a 24 hr time period. An assay of oxidative burst (30 min) and cytokine bioassays measuring IL-1, IL-6, and tumor necrosis factor (TNF) production (6-48 hr) were used to investigate short- and long-term activation of phagocytosing cells. Maximum myelin uptake by phagocytosing glial cells occurred within 12-24 hr following myelin incubation. Opsonization of myelin prior to the phagocytosis assay resulted in greater myelin uptake by mixed glial cell cultures, microglia, and THP-1 cells over that of nontreated myelin. The magnitude of myelin phagocytosis by astrocytes was considerably lower than microglia and THP-1, and was not affected by myelin opsonization. Within 30 min of myelin phagocytosis, microglia and THP-1 cells underwent oxidative burst; opsonization of myelin by purified anti-MBP IgG and heat-inactivated serum enhanced the microglial oxidative burst activity. Production of IL-1, TNF, and most markedly IL-6 by microglia was increased following 12-24 hr of myelin ingestion. Our data demonstrate that myelin phagocytosis by adult human-derived microglia occurs in vitro, is augmented when myelin is opsonized, and results in the activation of microglia as assessed by oxidative burst and cytokine production.

Adult↗

PubMed1995

Increased production of gelatinase B (matrix metalloproteinase-9) and interleukin-6 by activated rat microglia in culture.

Activated macrophages produce several matrix metalloproteinases (MMPs), a family of extracellular matrix (ECM)-degrading enzymes, during wound healing and in other inflammatory states. In response to brain injury, brain microglia become "activated," in a way similar to peripheral tissue macrophages, a process which includes differentiation and probably invasion and proliferation. Little is known about the ECM-degrading MMPs that are secreted by microglia upon activation. Thus, it was of interest to determine whether activated microglia secrete MMPs. Conditioned media samples obtained from cultured microglia that were stimulated with various activating agents were subjected to gelatin-substrate zymography. Microglia constitutively express low levels of a 94-kDa gelatinase (GLase) activity. Treatment with LPS, zymosan, and fixed Staphylococcus aureus for 24 hr stimulated the activity of the 94-kDa GLase, 4-20-fold, in a dose-dependent manner. Addition of INF gamma inhibited the LPS-stimulated activity of MMP-9. LPS, zymosan, and fixed Staphylococcus aureus also stimulated the secretion of IL-6 from microglia in a dose-dependent manner. The 94-kDa GLase activity was Ca++ dependent, it was inhibited by 1,10-phenanthroline, and it was activated by organomercurial compounds. When immunoblots were performed using specific antisera against the 94-kDa gelatinase B (MMP-9) with untreated and LPS-stimulated conditioned medium samples, a 94-kDa immunopositive band was observed. Thus, it appears that the 94-kDa GLase is gelatinase B (MMP-9). These results indicate that activators of peripheral macrophages are potent secretagogues for the MMPs in cultured microglia. The ability of activated microglia to secrete MMPs suggests that these enzymes may play an important function in the brain parenchyma during inflammatory states.

Animals↗

PubMed1997

Neuritic plaque evolution in Alzheimer's disease is accompanied by transition of activated microglia from primed to enlarged to phagocytic forms.

Activated microglia, overexpressing the potent neuroactive cytokine interleukin-1, have been implicated as a driving force in the evolution of diffuse amyloid deposits into diagnostic neuritic plaques in Alzheimer's disease. To evaluate this role further, we used double-label immunohistochemistry to classify and quantify plaque-associated and non-plaque-associated activated interleukin-1-immunoreactive microglia in parahippocampal tissue from 11 patients with Alzheimer's disease. These activated microglia were subclassified as primed (only slightly enlarged), enlarged, or phagocytic (enlarged with heterogeneous cytoplasmic contents). We further determined the distribution of these microglial subtypes among four defined plaque types. Most (84%) primed microglia were not plaque associated, although 13% were present in diffuse non-neuritic plaques and 3% were present in diffuse neuritic plaques. In contrast, most enlarged (55%) and phagocytic (91%) microglia were plaque associated. Of plaque-associated enlarged microglia, most (71%) were found in diffuse neuritic plaques with the remainder evenly distributed between diffuse non-neuritic and dense-core neuritic plaques (15% each). Of plaque-associated phagocytic microglia, a few were present in diffuse non-neuritic plaques (5%), but most were found in diffuse neuritic plaques (62%) and dense-core neuritic plaques (33%). These findings show preferential association of primed microglia with diffuse amyloid deposits and imply that microglial transformation from primed, to enlarged, to phagocytic types occurs in concert with the evolution of amyloid plaques from diffuse amyloid deposits to the neuritic beta-amyloid plaque forms in Alzheimer's disease. Microglial phagocytic activity in neuritic plaques may reflect involvement in the processing of diffuse amyloid into condensed beta-amyloid, or in clearance of neuritic debris.

Aged↗

PubMed2004

Mitochondria in activated microglia in vitro.

In the CNS, microglia become activated, i.e. change their functional state and phenotype, in response to a wide variety of pathological stimuli. Since this activation is triggered at a very low threshold and at the same time remains territorially restricted, the spatial distribution of activated microglia can be used as a sensitive, generic measure of the anatomical localisation of ongoing disease processes. One protein complex, undetectable in resting microglia but highly up-regulated upon activation in vivo and in vitro, is the 'peripheral benzodiazepine binding site', as measured by binding of the isoquinoline derivate PK11195. Particularly numerous in the outer membrane of mitochondria, this binding site has also been referred to as the 'mitochondrial benzodiazepine receptor'. The de novo expression of this receptor by activated microglia suggests that the process of activation may be associated with important qualitative changes in the state of mitochondria. Here, we provide confocal light- and electron microscopic evidence that the activation of microglia indeed entails conspicuous mitochondrial alterations. In cultured rat microglia stained with the fluorescent probe, JC-1, a sensitive indicator of mitochondrial membrane potential, we demonstrate that stimulation by bacterial lipopolysaccharide and interferon-gamma increases the number of microglial mitochondrial profiles and leads to marked changes in their morphology. Prominent elongated, "needle-like" mitochondria are a characteristic feature of activated microglia in vitro. Electron microscopically, an abundance of abnormal profiles, including circular cristae or ring- and U-shaped membranes, are found. Our observations support the notion that the previously reported increase in microglial binding of PK11195, that labelled with carbon-11 ([11C] (R)-PK11195) has clinical use for the visualisation of activated microglia in vivo by positron emission tomography, may at least in part relate to an increased number and altered functional state of microglial mitochondria.

Animals↗

PubMed1996

Selective induction of interleukin-6 in mouse microglia by granulocyte-macrophage colony-stimulating factor.

Astrocytes produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and support the survival and proliferation of microglia. To study the functions of GM-CSF in the central nervous system (CNS), we examined the effects of GM-CSF on cytokine production by glial cells. GM-CSF induced interleukin-6 (IL-6) production by microglia, but not by astrocytes, in a dose-dependent manner as assessed by bioassay and the detection of IL-6 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. GM-CSF did not induce tumor necrosis factor (TNF) alpha or IL-1 in microglia and astrocytes, whereas lipopolysaccharide induced all these cytokines. The induction of IL-6 by GM-CSF in microglia was completely inhibited by antibodies to GM-CSF. Neither IL-3 nor macrophage-CSF (M-CSF) induced IL-6 production in microglia. Given that IL-1 and TNF alpha, monokines derived from microglia, induce IL-6 production in astrocytes, but not in microglia, results indicate that astrocytes and microglia may mutually regulate IL-6 production by different cytokines.

Animals↗

PubMed1995

Keratan sulphate is a marker of differentiation of ramified microglia.

Recently we reported that the keratan sulphate epitope recognised by the monoclonal antibody 5D4 is expressed by a population of ramified microglia in adult rats. As ramified microglia is believed to differentiate from ameboid microglia during postnatal development, we studied the rat brain from birth to 90 postnatal days of life with the monoclonal antibody 5D4. Contrary to all the other microglia markers until now described, keratan sulphate is not expressed by ameboid microglia and by macrophages but appears on the surface of microglia only when the cells are differentiated and show ramified processes. The keratan sulphate positive cells become evident at different times in different central nervous system areas; the first were localised in the pyriform cortex and brainstem from the end of the second postnatal week. These observations suggest that keratan sulphate expression on microglia cells is induced by differentiation and by a resting functional state. Moreover the 5D4 monoclonal antibody showed a strong diffuse positive staining of some cortical, thalamic and white matter areas during the first two postnatal weeks. This staining was transient and it does not seem biologically correlated with the expression of the keratan sulphate on differentiated microglia.

Animals↗

PubMed1994

Interleukin-4 induces proliferation and activation of microglia but suppresses their induction of class II major histocompatibility complex antigen expression.

We recently found that microglia, brain macrophages, express interleukin-4 (IL-4) receptor mRNA in vitro. Since IL-4 exhibits a variety of functions on the cells of monocyte-macrophage lineage, we examined the effects of IL-4 on the functions of microglia. Recombinant IL-4 induced the proliferation of microglia in a dose- and time-dependent manner as determined by MTT colorimetric assay, [3H]thymidine uptake and bromodeoxyuridine (BrdU) incorporation. IL-4 also synergistically enhanced the proliferation of microglia with such colony-stimulating factors as IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). It also increased acid phosphatase activity and superoxide anion formation by these cells. Despite these positive effects on proliferation and activation, IL-4 suppressed the IFN gamma-induced class II MHC antigen expression in these cells. Since these effects of recombinant IL-4 were inhibited by the addition of monoclonal antibody against IL-4 receptors, the effects of IL-4 on microglia appear to be a specific function via IL-4 receptors. Although microglia and astrocytes produce a variety of immunoregulatory cytokines, neither cell produced IL-4 as determined by bioassay or detection of IL-4 mRNA by RT-PCR method. Thus, the exogenous IL-4 may contribute to the accumulation of microglia in or around inflammatory lesions in the central nervous system, and may be involved in the regulatory mechanisms of microglia.

Animals↗

PubMed1996

Human microglia activate lymphoproliferative responses to recall viral antigens.

The capacity of adult human microglia to activate memory T-lymphocyte responses to recall viral antigens in autologous peripheral blood lymphocytes (PBL) was examined using measles and influenza viruses. Microglia and peripheral blood macrophages were isolated form 6 patients who underwent surgical brain biopsies. Microglial cultures readily expressed high levels of HLA class II molecules under basal culture conditions. However, compared to macrophages, microglia appeared to express much lower levels of CD45, a phenotype that has been associated with the ability of rat brain macrophage/microglia to present antigen. PBL were depleted of macrophages (D-PBL) and the efficacy of the depletion was assessed by a reduction in the T-cell response to concanavalin A. D-PBL were reconstituted with macrophages, microglia, or in some cases microglia pretreated with interferon-gamma (IFN gamma). It was observed that microglia were as efficient as macrophages in presenting viral antigens. Pretreatment of microglia with IFN gamma did not enhance further antigen presentation. Oligodendrocytes which lack constitutive or inducible HLA class II molecules failed to present viral antigens. The results have implications of the direct function of microglia as perpetuators and possibly initiators of immune responses to virus infection in the central nervous system compartment.

Adult↗

PubMedDate not supplied

Role of microglia in senile plaque formation.

To assess the role of microglial cells in senile plaque (SP) formation, we examined the density and distribution of microglia in the temporal neocortex of three groups of nondemented individuals, chosen to represent sequential stages of SP formation (no SP, n = 14; diffuse plaques (DP) only, n = 12; both DP and neuritic plaques (NP), n = 14) and patients with Alzheimer's disease (AD, n = 11). The mean density of microglia was significantly greater in the AD group. In nondemented individuals, the presence of NP but not DP was associated with an increased number of microglial cells. Most NP (91%) were focally associated with microglial cells. DP less commonly contained microglia, however, individuals with some NP had microglia within a greater proportion of their DP (47%) than did those with only DP (19%). These findings suggest that: (a) microglia are not involved in the formation of DP; (b) the presence of NP is associated with both an overall increase in microglia and the focal aggregation of cells around NP; (c) microglia may be locally involved in the conversion of DP into NP. This final point represents the most significant aspect of this study, providing the first quantitative evidence to support a specific role for microglia in the formation of NP from DP.

Aged↗

PubMed1996

Expression of apolipoprotein E mRNA in rat microglia.

Apolipoprotein E (apoE) is a major risk factor for Alzheimer disease (AD), which is the most common cause of progressive dementing illness. ApoE has been postulated to be synthesized by astrocytes and taken up by microglia and neuronal cells. However, it remains unknown whether apoE is also produced by microglia in the brain. We analyzed apoE mRNA expression of microglia using a rat primary culture system. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed expression of apoE mRNA in cultured rat microglia. By RT-in situ-PCR, microglia showed positive staining for the PCR product of apoE mRNA. These results indicated that apoE was biosynthesized in rat microglia. We suggest that microglia might be one of the sources of apoE in the brain, and that apoE synthesized in microglia might be closely related to the pathogenesis of AD.

Animals↗