Microglia: A CNS-Specific Tissue Macrophage

Puntambekar, Shweta S.; Doose, Jonathan M.

doi:10.1007/978-0-387-73894-9_1

Cited by 7 publications

(6 citation statements)

References 47 publications

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“…Microglia, the myeloid-derived resident macrophages of the brain, play the primary role of immune surveillance and respond to environmental stress and immunological challenges (1, 2). Initial physical or pathogenic events in the CNS can trigger microglial expansion through recruitment of peripheral macrophages to the CNS, as a result of increased permeability of the BBB, differentiation from progenitor cells or proliferation of residual microglia (3).…”

Section: Introductionmentioning

confidence: 99%

Microglia Isolation from Adult Mouse Brain

Lee

Tansey

2013

Methods in Molecular Biology

127

102

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Although microglia isolation from embryonic or postnatal mouse brain is possible using a number of different protocols, microglia isolation from adult brain is more challenging and often results in low yields. Here, we describe a protocol to isolate intact microglia from adult mouse brain for functional assays, immunocytochemistry and/or flow cytometry analysis. This protocol involves enzymatic dissociation in medium supplemented with dispase II, papain and DNase I followed by mechanical dissociation. Cell separation is achieved via percoll gradients of various densities. Microglia isolated using this protocol is suitable for flow cytometry analysis, RNA isolation for gene expression by real-time PCR or microarrays, and for functional assays including cytokine production, chemotaxis and phagocytosis.

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Section: Introductionmentioning

confidence: 99%

Microglia Isolation from Adult Mouse Brain

Lee

Tansey

2013

Methods in Molecular Biology

127

102

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“…Microglia, the monocyte-derived resident macrophages of the brain, are primarily responsible for performing innate immune surveillance in the CNS (Puntambekar, 2008; Tansey, 2008). Microglia play a homeostatic role in the CNS and respond to environmental stresses and immunological challenges by scavenging excess neurotoxins and removing dying cells and cellular debris (Ransohoff and Perry, 2009).…”

Section: Introductionmentioning

confidence: 99%

Regulator of G-Protein Signaling-10 Negatively Regulates NF-κB in Microglia and Neuroprotects Dopaminergic Neurons in Hemiparkinsonian Rats

Lee¹,

Chung²,

McAlpine³

et al. 2011

J. Neurosci.

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Microglia are the brain-resident macrophages responsible for immune surveillance that become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Previous work from our group demonstrated that mice deficient in Regulator of G-protein Signaling 10 (RGS10), a microglia-enriched GTPase activating protein (GAP) for G-protein alpha subunits, displayed increased microglial burden in the CNS at birth and developed a parkinsonian phenotype after exposure to chronic systemic inflammation, implicating a neuroprotective role for RGS10 in the nigrostriatal pathway. While it is known that RGS10 is expressed in both microglia and certain subsets of neurons, it is not known whether RGS10 functions similarly in both cells types. In this study we sought to delineate the specific role of RGS10 in microglia and identify the molecular pathway(s) required for RGS10 to exert its actions in microglia. Here, we identify RGS10 as a negative regulator of the NF-κB pathway in microglia and demonstrate that the pro-inflammatory and cytotoxic phenotype of Rgs10-null microglia can be reversed by lentiviral-mediated restoration of RGS10 expression. In vivo gene transfer of RGS10 into the substantia nigra pars compacta (SNpc) of rats reduced microgliosis and protected against 6-OHDA neurotoxin-induced death of dopaminergic (DA) neurons. Together, our findings suggest that modulation of RGS10 activity in microglia may afford therapeutic benefit in the treatment of chronic neuroinflammatory conditions as well as neuroprotection against inflammation-related degeneration in Parkinson’s disease (PD), the second most common neurodegenerative disorder affecting individuals over age 65.

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“…They regulate the innate immune response, communicate with other brain cells, and act as scavengers by removing dying cells [2, 3]. Any insult to the brain, exogenous or endogenous, that disturbs its homeostasis leads to microglial activation.…”

Section: Introductionmentioning

confidence: 99%

RNF11 modulates microglia activation through NF-κB signalling cascade

Dalal

Pranski

Tansey

et al. 2012

Neuroscience Letters

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Microglia are resident macrophages in the central nervous system (CNS) that play a major role in neuroinflammation and pathogenesis of several neurodegenerative diseases. Upon activation, microglia releases a multitude of pro-inflammatory factors that initiate and sustain an inflammatory response by activating various signalling pathways, including the NF-κB pathway in a feed forward cycle. In microglial cells, activation of NF-κB signalling is normally transient, while sustained NF-κB activation is associated with persistent neuroinflammation. RING finger protein 11 (RNF11), in association with A20 ubiquitin-editing complex, is one of the key negative regulators of NF-κB signalling pathway in neurons. In this study, we have demonstrated and confirmed this role of RNF11 in microglia, the immune cells of the CNS. Coimmunoprecipitation experiments showed that RNF11 and A20 interact in a microglial cell line, suggesting the presence of A20 ubiquitin-editing protein complex in microglial cells. Next, using targeted short hairpin RNA (shRNA) knockdown and over-expression of RNF11, we established that RNF11 expression levels are inversely related to NF-κB activation, as evident from altered expression of NF-κB transcribed genes. Moreover our studies, illustrated that RNF11 confers protection against LPS-induced cell cytotoxicity. Thus our investigations clearly demonstrated that microglial RNF11 is a negative regulator of NF-κB signalling pathway and could be a strong potential target for modulating inflammatory responses in neurodegenerative diseases.

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Microglia: A CNS-Specific Tissue Macrophage

Cited by 7 publications

References 47 publications

Microglia Isolation from Adult Mouse Brain

Microglia Isolation from Adult Mouse Brain

Regulator of G-Protein Signaling-10 Negatively Regulates NF-κB in Microglia and Neuroprotects Dopaminergic Neurons in Hemiparkinsonian Rats

RNF11 modulates microglia activation through NF-κB signalling cascade

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