Characterization of a novel brain‐derived microglial cell line isolated from neonatal rat brain

Cheepsunthorn, Poonlarp; Radov, L. A.; Menzies, S. L.; Reid, John D.; Connor, James R.

doi:10.1002/glia.1070

Cited by 148 publications

(123 citation statements)

References 46 publications

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“…Plaques eventually developed in the hippocampus at a later age. In contrast, OVX APP23 mice did not display plaques until they reached 9 months of age or older, which is consistent with other reports (38,39). Taken together, these results suggest that brain estrogen deficiency accelerates A␤ plaque formation.…”

Section: Discussionsupporting

confidence: 92%

“…We observed no qualitative difference in plaque size and density between OVX and APP23 mice ( Fig. 2 E and D), which is consistent with the findings of other studies (38,39). Widely distributed A␤ plaques with or without a distinct core were observed in the hippocampus and cortex of APP23͞Ar ϩ/Ϫ mice (Fig.…”

Section: App23 Mice With An Aromatase Gene Knockout (App23͞ar ؉/؊ ) Havesupporting

confidence: 92%

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Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer's disease animal model

Yue

Lu²,

Lancaster³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

333

306

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Much evidence indicates that women have a higher risk of developing Alzheimer's disease (AD) than do men. The reason for this gender difference is unclear. We hypothesize that estrogen deficiency in the brains of women with AD may be a key risk factor. In rapidly acquired postmortem brains from women with AD, we found greatly reduced estrogen levels compared with those from age-and gender-matched normal control subjects; AD and control subjects had comparably low levels of serum estrogen. We examined the onset and severity of AD pathology associated with estrogen depletion by using a gene-based approach, by crossing the estrogen-synthesizing enzyme aromatase gene knockout mice with APP23 transgenic mice, a mouse model of AD, to produce estrogen-deficient APP23 mice. Compared with APP23 transgenic control mice, estrogen-deficient APP23 mice exhibited greatly reduced brain estrogen and early-onset and increased ␤ amyloid peptide (A␤) deposition. These mice also exhibited increased A␤ production, and microglia cultures prepared from the brains of these mice were impaired in A␤ clearance͞degradation. In contrast, ovariectomized APP23 mice exhibited plaque pathology similar to that observed in the APP23 transgenic control mice. Our results indicate that estrogen depletion in the brain may be a significant risk factor for developing AD neuropathology.amyloid deposition ͉ aromatase ͉ transgenic animal N europathological hallmarks of Alzheimer's disease (AD) include significant deposition of extracellular ␤ amyloid peptide (A␤) and presence of neurofibrillary tangles in the brain (1). A␤ is derived from the two-step enzymatic processing of amyloid precursor protein (APP) in which ␤-secretase (BACE) cleaves the ␤-site of APP to release the N terminus of A␤, and the ␥-secretase protein complex cleaves the ␥-site of APP to release the C terminus of A␤ (2, 3). Overproduction and progressive deposition of A␤ are known to underlie, in part, A␤ plaque formation, a key pathologic feature of AD. The initial cleavage of APP by BACE is critical for A␤ associated with AD neuropathology (4). Recent studies have shown that BACE activity increases with age and is elevated in AD brains (5, 6).Impaired A␤ clearance and͞or degradation may also contribute to A␤ plaque formation. Our previous findings support this hypothesis: Microglia isolated from AD brains have impaired phagocytic activity, leading to reduced A␤ clearance (7). Other groups have found that cytoplasmic A␤ granules in the plaque-associated glia and microglia participate in the clearance of A␤ in A␤-immunized AD patients and APP transgenic mice (8, 9).Two enzymes are involved in A␤ degradation and clearance: insulin-degrading enzyme (IDE) and neprilysin (NEP). IDE is expressed in high concentrations in the brain. Besides degrading insulin and several regulatory peptides, IDE also degrades the intracellular domain of APP and is responsible for degrading and clearing A␤ from the brain (10, 11). Indeed, genetic linkage studies have shown that late-onset AD loci on chromosome 1...

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Section: Discussionsupporting

confidence: 92%

Section: App23 Mice With An Aromatase Gene Knockout (App23͞ar ؉/؊ ) Havesupporting

confidence: 92%

Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer's disease animal model

Yue

Lu²,

Lancaster³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

333

306

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“…Unstimulated and LPS -treated cells displayed morphological signatures of microglia, as seen in previous studies [22,[27][28][29] , which included smaller bodies and elongated processes, or amoeboidshaped and rounder cellular bodies, respectively. This demonstrates that CHME-5 cells retain characteristics that define their role as microglial cells.…”

Section: Discussionsupporting

confidence: 77%

LPS-induced TLR4 neuroinflammatory signaling in CHME-5 microglial cells

Figueroa-Hall¹,

Anderson²,

Das³

et al. 2017

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Aim:In the field of neuroinflammation, identifying specific effects of pharmacological agents and other factors is problematic given the relative difficulty and expense in obtaining and culturing primary microglia. Immortalized microglial cell lines are very useful, but only a limited number have been characterized for inflammatory signaling. Therefore, characterization of lipopolysaccharide (LPS)-induced toll-like receptor 4 (TLR4) signaling in CHME-5, a microglial cell line, is expected to be of value as an experimental model of inflammatory signaling in the central nervous system (CNS). Methods: It was recently suggested that CHME-5 cells are of rat origin, not human, hence, verification of this claim using short tandem repeat genotype sequencing, along with immunoblotting, reverse transcription-polymerase chain reaction, and immunocytochemistry techniques to validate that CHME-5 retain morphological, phenotypical, and functional characteristics of primary microglia were undertaken. Results: LPS induced inhibitor kappa B-alpha and nuclear factorkappa B (NF-κB) p65 activation, NF-κB p65 binding activity, and tumor necrosis factor alpha gene expression. Additionally, results also confirmed the maintenance of microglial phenotype as seen with increased cluster of differentiation 68 gene and protein expression, immunofluorescence, and the absence of glial fibrillary acidic protein-immunoreactivity. Key words:Escherichia coli lipopolysaccharide, nuclear factor-kappa B p65, cluster of differentiation 68, toll-like receptor 4, neuroinflammation ABSTRACTArticle history:

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“…Cells were cultured in MEM containing 10% FBS (Sigma-Aldrich), 1.4 mM glutamine, and 20 M 2-ME (Sigma-Aldrich). Rat HAPI microglial cells were provided by J. Connor (Pennsylvania State University, State College, PA) (39). HAPI cells were cultured in DMEM containing 5% FBS, 1.4 mM glutamine, and 100 U/ml penicillin plus 100 g/ml streptomycin (Life Technologies/BRL, Grand Island, NY).…”

Section: Cell Culture Of Microgliamentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-γ Agonist 15-Deoxy-Δ12,1412,14-Prostaglandin J2 Ameliorates Experimental Autoimmune Encephalomyelitis

Diab¹,

Deng²,

Smith³

et al. 2002

The Journal of Immunology

278

221

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Peroxisome proliferator-activated receptors (PPAR) are members of a nuclear hormone receptor superfamily that includes receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Previous studies dealing with PPAR-γ expression in the immune system have been limited. Recently, PPAR-γ was identified in monocyte/macrophage cells. In this study we examined the role of PPAR-γ in experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis. The hypothesis we are testing is whether PPAR-γ plays an important role in EAE pathogenesis and whether PPAR-γ ligands can inhibit the clinical expression of EAE. Initial studies have shown that the presence of the PPAR-γ ligand 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) inhibits the proliferation of Ag-specific T cells from the spleen of myelin basic protein Ac1–11 TCR-transgenic mice. 15d-PGJ2 suppressed IFN-γ, ΙL-10, and IL-4 production by both Con A- and myelin basic protein Ac1–11 peptide-stimulated lymphocytes as determined by ELISA and ELISPOT assay. Culture of encephalitogenic T cells with 15d-PGJ2 in the presence of Ag reduced the ability of these cells to adoptively transfer EAE. Examination of the target organ, the CNS, during the course of EAE revealed expression of PPAR-γ in the spinal cord inflammatory infiltrate. Administration of 15d-PGJ2 before and at the onset of clinical signs of EAE significantly reduced the severity of disease. These results suggest that PPAR-γ ligands may be a novel therapeutic agent for diseases such as multiple sclerosis.

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Characterization of a novel brain‐derived microglial cell line isolated from neonatal rat brain

Cited by 148 publications

References 46 publications

Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer's disease animal model

Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer's disease animal model

LPS-induced TLR4 neuroinflammatory signaling in CHME-5 microglial cells

Peroxisome Proliferator-Activated Receptor-γ Agonist 15-Deoxy-Δ12,1412,14-Prostaglandin J2 Ameliorates Experimental Autoimmune Encephalomyelitis

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