Interesting Study on the importance of Leukotriene B4 for differentiation of Neural Stem Cells into Neurons
Just doing some googling on leukotrienes and lipoxins and ran across this study. If the findings are correct, it might also indicate that caution might be warranted in using 5-LOX inhibitors and Leukotriene B4 blockers in CNS disease:
Some interesting quotes from the article:
"Here we describe for the first time the potent neuronal regulatory functions of these bioactive LOX products. Activation of the LTB4 signaling pathways in NSC by physiological levels of LTB4 promoted stem cell proliferation. Excessive activation of LTB4 signaling, with higher concentrations of LTB4 (>3 µM), resulted in inhibition of NSC growth. This biphasic action of LTB4 suggests that LTB4 signaling tightly regulates proliferation of NSCs and indicates that optimal amounts in vivo of local LTB4 might play a role in NSC survival and proliferation.
Consistent with this role of LTB4 signaling in regulating NSC proliferation, 5-lipoxygenase inhibitors and LTB4 receptor antagonist caused apoptosis of NSCs. It is of note that proliferation of human neuronal precursor cells was also blocked by 5-lipoxygenase inhibitor (25) . These results suggest that LTB4 signaling regulates NSC growth and that programmed cell death ensues in its absence."
"Of particular interest, LTB4 stimulated the differentiation of NSCs into neurons. This was confirmed by increased neurite outgrowth and increased expression of MAP2, as well as by increased expression of several channels and receptors, such as voltage-gated sodium channel, potassium channel, chloride channel, and nicotinic receptor. Increased levels of these molecules are required for the maturation of differentiated neurons. The present results indicate that LTB4 signals not only proliferation, but also differentiation of NSCs into neurons. In general, it is rare to observe markers of both proliferation and differentiation at the same stage in somatic cells. The mechanisms underlying stimulation of differentiation by LTB4 may differ from those required for proliferation. NSCs are considered multipotent cells that have the ability of both "self-renewal" and "differentiation." Therefore, it might be unique to the NSC system to exhibit both proliferation and differentiation phenotypes in response to LTB4.
Visible disorders were not observed for 5-lipoxygenase knockout mice during development, although various different responses against inflammation and other pathological conditions were observed with 5-lipoxygenase knockout mice compared with those of wild-type (WT) mice (27 28 29) . These reports and our observations in the present study indicate that bioactions of 5-lipoxygenase-derived lipid mediators described in this study may be more relevant in pathophysiological conditions such as PD, Huntington’s disease, nerve injury, stroke, and multiple sclerosis than for normal CNS development and maturation."
See more about 5-LOX inhibitors and Leukotriene B4 blockers here: