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Microglia: Neuroprotective and Neurodestructive Properties

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Handbook of Neurotoxicity

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Abstract

In the central nervous system, resident macrophages, microglia, and perivascular macrophages perform similar functions to peripheral macrophages yet display highly specialized features. They maintain some phenotypic characteristics and lineage-related properties common to their cells of origin and their rapid response in areas of neuronal death led to the contention that microglia serve as brain macrophages. While microglia are often considered the immune cell of the brain, they also show distinct features that make them unique from other tissue macrophages. They are maintained in a relatively quiescent and monitoring state by regulatory factors released by neurons and astrocytes. Via contact-dependent and receptor-dependent signaling, microglia rapidly respond to various events in the brain in an effort to return the microenvironment to homeostasis, to assist in refining the neural network during development and with repair, and to remove excess and aberrant proteins. Depending on the nature of the response and the physiological function of the microglia, a release of immune-related signaling factors can accompany a morphological change. It was initially thought that the immune-related response of microglia mirrors that of peripheral macrophages and considered to be adverse to the nervous system. However, further evaluation of these cells suggests that overall their responses are ones critical to the maintenance and function of the nervous system. This chapter will serve to set the framework for evaluating the microglia within the context of data available on their varied functions within the nervous system.

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Abbreviations

AD:

Alzheimer’s disease

AMPA:

Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid

ApoE:

Apolipoprotein

ATP:

Adenosine triphosphate

Aβ42 :

Amyloid-beta 42

BBB:

Blood–brain barrier

Ca2+ :

Calcium

CNS:

Central nervous system

COX:

Cyclooxygenase

CR:

Complement receptor

CSF:

Colony-stimulating factor

CX3CL1:

Fractalkine

DAMPs:

Danger-associated molecular patterns

Fc:

Fragment, crystallizable region

HO-1:

Heme oxygenase-1

HSP:

Heat shock protein

IFN:

Interferon

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharide

mGluR:

Metabotropic glutamate receptor

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

MPP+:

1-methyl-4-phenylpyridinium

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NF-κB:

Nuclear factor kappa B

NLRs:

NOD-like receptors

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOX2:

NADPH oxidase

P2:

Purinergic

PAMPs:

Pathogen-associated molecular patterns

PD:

Parkinson’s disease

PRRs:

Pattern recognition receptors

RAGE:

Receptor for advanced glycation end products

RNS:

Nitric oxide-dependent reactive nitrogen species

ROS:

Reactive oxygen species

SN:

Substantia nigra

TGF:

Transforming growth factor

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TREM-2:

Triggering receptor expressed on myeloid cells-2

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Acknowledgments

This work was funded by the Division of Intramural Research and the National Toxicology Program Laboratory, National Institute of Environmental Health Sciences (NIEHS), and National Institutes of Health (NIH). Statements, opinions, or conclusions contained therein do not necessarily represent those of NIEHS, NIH, or the United States government.

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  1. Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, 111 T. W. Alexander Drive, 27709, Research Triangle Park, NC, USA

    G. Jean Harry & Christopher A. McPherson

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  1. G. Jean Harry
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  2. Christopher A. McPherson
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Correspondence to G. Jean Harry .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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Harry, G.J., McPherson, C.A. (2014). Microglia: Neuroprotective and Neurodestructive Properties. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_55

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