What is it about?

Microglia are immunocompetent cells specifically expressed in the central nervous system. The involvement of microglia in neuropsychiatric disorders such as schizophrenia is suggested well. The activation of such microglia has been shown to be modulated by various factors, one of which is fractalkine. In this paper, we found that various inflammatory stimuli attenuate fractalkine signaling by decreasing the expression of its receptors.

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Why is it important?

With regard to fractalkine, a signal that attenuates the immune response, once stress and psychiatric disorders develop, fractalkine receptors that attenuate the immune response in microglia are reduced, which may result in poor subsequent therapeutic effects.


The term “stress resilience” has become more common in medical biology papers in the last decade or so. It appears to be related not only to the development of neuropsychiatric disorders but also to exacerbations of Alzheimer’s disease and post-stroke neurodegeneration, and its detailed molecular pathology is expected to be elucidated for the treatment of neurological diseases. Fractalkine signaling is a signal involved in the immune response of microglia that affects stress resilience. Microglia express an fractalkine receptor, CX3CR1, and exchange signals with ligand-expressing neurons and other cells. The amount and form of the ligand fractalkine can inflect the stimulation of microglia and modulate its effects, ultimately modifying brain and nerve functions. Changes in CX3CR1 expression in microglia have been reported often, and it is generally accepted that its expression is altered by various stimuli, which may also occur in human diseases. Unfortunately, however, there is currently no clear direction as to whether this variation is uniformly good or bad for certain conditions. Nonetheless, this also being the case in humans, if we can prove beneficial changes in CX3CR1 for each individual disease by adjusting the life environment outside of clinical treatment, such as diet and exercise, then we may be able to acquire beneficial stress resilience through fractalkine signaling.

Koichi Inoue
Nagoya Shiritsu Daigaku

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This page is a summary of: Modulation of inflammatory responses by fractalkine signaling in microglia, PLoS ONE, May 2021, PLOS,
DOI: 10.1371/journal.pone.0252118.
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