Histamine and Microglia

This article from Journal of Neuroinflammation caught my eye …

Histamine modulates microglia function

http://www.jneuroinflammation.com/content/9/1/90/abstract

(A provisional PDF is available at that link)

“Histamine is commonly acknowledged as an inflammatory mediator in peripheral tissues, leaving its role in brain immune responses scarcely studied. Therefore, our aim was to uncover the cellular and molecular mechanisms elicited by this molecule and its receptors in microglia-induced inflammation by evaluating cell migration and inflammatory mediator release.

Methods

Firstly, we detected the expression of all known histamine receptor subtypes (H1R, H2R, H3R and H4R), using a murine microglial cell line and primary microglia cell cultures from rat cortex, by real-time PCR analysis, immunocytochemistry and Western blotting. Then, we evaluated the role of histamine in microglial cell motility by performing scratch wound assays. Results were further confirmed using murine cortex explants. Finally, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels were evaluated by ELISA measurements to determine the role of histamine on the release of these inflammatory mediators.

Results

After 12 h of treatment, 100 muM histamine and 10 mug/ml histamine-loaded poly (lactic-co-glycolic acid) microparticles significantly stimulated microglia motility via H4R activation. In addition, migration involves alpha5beta1 integrins, and p38 and Akt signaling pathways. Migration of microglial cells was also enhanced in the presence of lipopolysaccharide (LPS, 100 ng/ml), used as a positive control. Importantly, histamine inhibited LPS-stimulated migration via H4R activation. Histamine or H4R agonist also inhibited LPS-induced IL-1beta release in both N9 microglia cell line and hippocampal organotypic slice cultures.

Conclusions

To our knowledge, we are the first to show a dual role of histamine in the modulation of microglial inflammatory responses. Altogether, our data suggest that histamine per se triggers microglia motility, whereas histamine impedes LPS-induced microglia migration and IL-1beta release. This last datum assigns a new putative anti-inflammatory role for histamine, acting via H4R to restrain exacerbated microglial responses under inflammatory challenge, which could have strong repercussions in the treatment of CNS disorders accompanied by microglia-derived inflammation.”

I believe that this may lead to a new direction in therapeutic treatments in Autism. I will certainly be following further research in this area.

Further readings

Johns Hopkins Neuroimmunopathology

The meaning of neuroinflammatory findings in autism

http://www.neuro.jhmi.edu/neuroimmunopath/autism_faqs.htm

Image: dream designs / FreeDigitalPhotos.net

This entry was posted in Autism, co-morbid, Epigenetics, General, Immune System, Inflammation, Neurology, Physiology, Treatment. Bookmark the permalink.

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