Abstract
Cyclooxygenases catalyze the first committed step in the formation of prostaglandins and thromboxanes from arachidonic acid. Cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, is expressed in brain selectively in neurons of hippocampus, cerebral cortex, amygdala, and hypothalamus. Prostaglandins function in many processes in the CNS, including fever induction, nociception, and learning and memory, and are upregulated in paradigms of excitotoxic brain injury such as stroke and epilepsy. To address the varied functions of COX-2 and its prostaglandin products in brain, we have developed a transgenic mouse model in which COX-2 is selectively overexpressed in neurons of the CNS. COX-2 transgenic mice demonstrate elevated levels of all prostaglandins and thromboxane, albeit with a predominant induction of PGE2 over other prostaglandins, followed by more modest inductions of PGI2, and relatively smaller increases in PGF2α, PGD2, and TxB2. We also examined whether increased neuronal production of prostaglandins would affect fever induction in response to the bacterial endotoxin lipopolysaccharide. COX-2 induction in brain endothelium has been previously determined to play an important role in fever induction, and we tested whether neuronal expression of COX-2 in hypothalamus also contributed to the febrile response. We found that in mice expressing transgenic COX-2 in anterior hypothalamus, the febrile response was significantly potentiated in transgenic as compared to non-transgenic mice, with an accelerated onset of fever by 1–2 hours after LPS administration, suggesting a role for neuronally derived COX-2 in the fever response.
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Vidensky, S., Zhang, Y., Hand, T. et al. Neuronal overexpression of COX-2 results in dominant production of PGE2 and altered fever response. Neuromol Med 3, 15–27 (2003). https://doi.org/10.1385/NMM:3:1:15
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DOI: https://doi.org/10.1385/NMM:3:1:15