Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain

Lawson, L.J.; Perry, V.H.; Dri, Pietro; Gordon, Siamon

doi:10.1016/0306-4522(90)90229-w

Cited by 1,731 publications

(1,339 citation statements)

References 42 publications

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“…Microglia are present throughout the brain and are higher in the substantia nigra (12% of cells) than in the cortex (only 5%) (Kim et al, 2000;Lawson et al, 1990). In PD patients, the substantia nigra was found to have more than 6-time the number of reactive microglia as compared to the control brains (McGeer et al, 1988a;McGeer et al, 1988b).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Miller

Sun

2007

Brain Research

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Excess production of reactive oxygen species (ROS) is an important mechanism underlying the pathogenesis of a number of neurodegenerative diseases including Parkinson's disease (PD) which is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Exposure to paraquat, an herbicide with structure similar to the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP + ), has been shown to produce PD-like symptoms. Despite previous focus on the dopaminergic neurons and signaling pathways involved in their cell death, recent studies have implicated microglial cells as a major producer of ROS for damaging neighboring neurons. In this study, we examined the source of ROS and the underlying signaling pathway for paraquat-induced cytotoxicity to BV-2 microglial cells. Paraquat-induced ROS production (including superoxide anions) in BV-2 cells was accompanied by translocation of the p67phox cytosolic subunit of NADPH oxidase to the membrane. Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol. Apocynin and DPI also rescued cells from paraquat-induced toxicity. The inhibitors for protein kinase C delta (PKCδ) or extracellular signal-regulated kinases (ERK1/2) could partially attenuate paraquat-induced ROS production and cell death. Rottlerin, a selective PKCδ inhibitor, also inhibited paraquat-induced translocation of p67phox. Taken together, this study demonstrates the involvement of ROS from NADPH oxidase in mediating paraquat cytotoxicity in BV-2 microglial cells and this process is mediated through PKCδ-and ERK-dependent pathways.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Miller

Sun

2007

Brain Research

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“…Microglia comprise around 5-12% of the cells in the CNS and are heterogeneously distributed (Lawson et al, 1990). They originate from bone marrow-derived monocytes migrating during perinatal time (Nakajima & Kohsaka, 2001).…”

Section: Microglia Activation and Proliferation In The Spinal Cord Inmentioning

confidence: 99%

Do glial cells control pain?

Wen²,

et al. 2007

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Management of chronic pain is a real challenge, and current treatments focusing on blocking neurotransmission in the pain pathway have only resulted in limited success. Activation of glia cells has been widely implicated in neuroinflammation in the central nervous system, leading to neruodegeneration in many disease conditions such as Alzheimer's and multiple sclerosis. The inflammatory mediators released by activated glial cells, such as tumor necrosis factor-α and interleukin-1β can not only cause neurodegeneration in these disease conditions, but also cause abnormal pain by acting on spinal cord dorsal horn neurons in injury conditions. Pain can also be potentiated by growth factors such as BDNF and bFGF that are produced by glia to protect neurons. Thus, glia cells can powerfully control pain when they are activated to produce various pain mediators. We will review accumulating evidence supporting an important role of microglia cells in the spinal cord for pain control under injury conditions (e.g. nerve injury). We will also discuss possible signaling mechanisms in particular MAP kinase pathways that are critical for glia control of pain. Investigating signaling mechanisms in microglia may lead to more effective management of devastating chronic pain.

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“…Microglial cells appear in all regions of the mature CNS, although their density varies between areas of the nervous parenchyma (Lawson et al, 1990). Two mechanisms may contribute to the spreading of microglial cells throughout the nervous parenchyma: proliferation and migration.…”

Section: Spreading Of Microglial Precursors Within the Cns: Proliferamentioning

confidence: 99%

“…However, the distribution of microglial cells during development frequently does not coincide with intense cell death (Milligan et al, 1991a;Cuadros et al, 1994Cuadros et al, , 1997Parnaik et al, 1996), and no relationship was found between the density of microglial cells and the intensity of cell death in particular regions during development (Lawson et al, 1990). Therefore, other factors in addition to degeneration phenomena must also participate in controlling migration.…”

Section: Factors That Control Migration Of Microglial Cellsmentioning

confidence: 99%

“…It has been suggested that the variability in microglial cells in di erent regions of the brain depends on environmental factors (Lawson et al, 1990;Sievers et al, 1996;Vela et al, 1995). Microglial cells in regions exposed to plasma proteins are less rami®ed than microglia in regions of the brain parenchyma with a complete blood±brain barrier which excludes plasma proteins (Perry and Gordon, 1991).…”

Section: Differentiation Of Microglial Cellsmentioning

confidence: 99%

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The origin and differentiation of microglial cells during development

Cuadros

Navascués

1998

Progress in Neurobiology

266

175

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AbstractÐSome authors claim that microglia originate from the neuroepithelium, although most now believe that microglial cells are of mesodermal origin, and probably belong to the monocyte/macrophage cell line. These cells must enter the developing central nervous system (CNS) from the blood stream, the ventricular space or the meninges. Afterward microglial cells are distributed more or less homogeneously through the entire nervous parenchyma. Stereotyped patterns of migration have been recognized during development, in which long-distance tangential migration precedes radial migration of individual cells. Microglial cells moving through the nervous parenchyma are ameboid microglia, which apparently di erentiate into rami®ed microglia after reaching their de®nitive location. This is supported by the presence of cells showing intermediate features between those of ameboid and rami®ed microglia. The factors that control the invasion of the nervous parenchyma, migration within the developing CNS and di erentiation of microglial cells are not well known. These phenomena apparently depend on environmental factors such as soluble or cell-surface bound molecules and components of the extracellular matrix. Microglial cells within the developing CNS are involved in clearing cell debris and withdrawing misdirected or transitory axons, and presumably support cell survival and neurite growth. #

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Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain

Cited by 1,731 publications

References 42 publications

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Do glial cells control pain?

The origin and differentiation of microglial cells during development

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