Microglia as a source and target of cytokines.
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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.read more
Citations
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A Meta-Analysis of Cytokines in Major Depression
Yekta Dowlati,Nathan Herrmann,Nathan Herrmann,Walter Swardfager,Walter Swardfager,Helena Liu,Lauren Sham,Elyse K. Reim,Krista L. Lanctôt,Krista L. Lanctôt +9 more
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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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.
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P2x4 receptors induced in spinal microglia gate tactile allodynia after nerve injury
Makoto Tsuda,Yukari Shigemoto-Mogami,Schuichi Koizumi,Akito Mizokoshi,Shinichi Kohsaka,Michael W. Salter,Kazuhide Inoue +6 more
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.
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