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Perinatal hypoxia-ischemia reduces 7 nicotinic receptor expression and selective 7 nicotinic receptor stimulation suppresses inflammation and promotes microglial Mox phenotype

Hua, S;Ek, CJ;Mallard, C;Johansson, ME;

Inflammation plays a central role in neonatal brain injury. During brain inflammation the resident macrophages of the brain, the microglia cells, are rapidly activated. In the periphery, 7 nicotinic acetylcholine receptors ( 7R) present on macrophages can regulate inflammation by suppressing cytokine release. In the current study we investigated 7R expression in neonatal mice after hypoxia-ischemia (HI). We further examined possible anti-inflammatory role of 7R stimulation in vitro and microglia polarization after 7R agonist treatment. Real-time PCR analysis showed a 33% reduction in 7R expression 72h after HI. Stimulation of primary microglial cells with LPS in combination with increasing doses of the selective 7R agonist AR-R 17779 significantly attenuated TNF release and increased 7R transcript in microglial cells. Gene expression of M1 markers CD86 and iNOS, as well as M2 marker CD206 was not influenced by LPS and/or 7R agonist treatment. Further, Mox markers heme oxygenase (Hmox1) and sulforedoxin-1 (Srx1) were significantly increased, suggesting a polarization towards the Mox phenotype after 7R stimulation. Thus, our data suggest a role for the 7R also in the neonatal brain and support the anti-inflammatory role of 7R in microglia, suggesting that 7R stimulation could enhance the polarization towards a reparative Mox phenotype.

  • PubMed ID: 24757672