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Microglia as a source and target of cytokines.

Uwe-Karsten Hanisch
- 01 Nov 2002 - 
- Vol. 40, Iss: 2, pp 140-155
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TLDR
Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context.
Abstract
Cytokines constitute a significant portion of the immuno- and neuromodulatory messengers that can be released by activated microglia. By virtue of potent effects on resident and invading cells, microglial cyto- and chemokines regulate innate defense mechanisms, help the initiation and influence the type of immune responses, participate in the recruitment of leukocytes to the CNS, and support attempts of tissue repair and recovery. Microglia can also receive cyto- and chemokine signals as part of auto- and paracrine communications with astrocytes, neurons, the endothelium, and leukocyte infiltrates. Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context. In principle, microglial activation aims at CNS protection. However, failed microglial engagement due to excessive or sustained activation could significantly contribute to acute and chronic neuropathologies. Dysregulation of microglial cytokine production could thereby promote harmful actions of the defense mechanisms, result in direct neurotoxicity, as well as disturb neural cell functions as they are sensitive to cytokine signaling.

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Journal ArticleDOI

A Meta-Analysis of Cytokines in Major Depression

TL;DR: A meta-analysis of studies measuring cytokine concentration in patients with major depression reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects, strengthening evidence that depression is accompanied by activation of the IRS.
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Physiology of Microglia

TL;DR: Current studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains, and microglial cells are considered the most susceptible sensors of brain pathology.
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Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia

TL;DR: Onset and progression of amyotrophic lateral sclerosis represent distinct disease phases defined by mutant action within different cell types to generate non–cell-autonomous killing of motor neurons; these findings validate therapies, including cell replacement, targeted to the non-neuronal cells.
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Inflammation is detrimental for neurogenesis in adult brain.

TL;DR: It is demonstrated that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats, raising the possibility that suppression of hippocampal Neurogenesis by activatedmicroglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.
Journal ArticleDOI

P2x4 receptors induced in spinal microglia gate tactile allodynia after nerve injury

TL;DR: It is demonstrated that activation of P2X4Rs in hyperactive microglia is necessary for tactile allodynia after nerve injury and is sufficient to produce tactileAllodynia in normal animals, suggesting that blocking P1X4 receptors in microglial might be a new therapeutic strategy for pain induced by nerve injury.
References
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Journal ArticleDOI

Death receptors: signaling and modulation

Avi Ashkenazi, +1 more
- 28 Aug 1998 - 
TL;DR: Apoptosis is a cell suicide mechanism that enables metazoans to control cell number in tissues and to eliminate individual cells that threaten the animal's survival.
Journal ArticleDOI

Microglia: a sensor for pathological events in the CNS

TL;DR: An understanding of intercellular signalling pathways for microglia proliferation and activation could form a rational basis for targeted intervention on glial reactions to injuries in the CNS.
Journal ArticleDOI

Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.

TL;DR: It is reported that immunization of the young animals essentially prevented the development of β-amyloid-plaque formation, neuritic dystrophy and astrogliosis, and treatment of the older animals markedly reduced the extent and progression of these AD-like neuropathologies.
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