Perinatal hypoxia-ischemia reduces α 7 nicotinic receptor expression and selective α 7 nicotinic receptor stimulation suppresses inflammation and promotes microglial Mox phenotype.
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, α 7 nicotinic acetylcholine receptors ( α 7R) present on macrophages can regulate inflammation by suppressing cytokine release. In the current study we investigated α 7R expression in neonatal mice after hypoxia-ischemia (HI). We further examined possible anti-inflammatory role of α 7R stimulation in vitro and microglia polarization after α 7R agonist treatment. Real-time PCR analysis showed a 33% reduction in α 7R expression 72 h after HI. Stimulation of primary microglial cells with LPS in combination with increasing doses of the selective α 7R agonist AR-R 17779 significantly attenuated TNF α release and increased α 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 α 7R agonist treatment. Further, Mox markers heme oxygenase (Hmox1) and sulforedoxin-1 (Srx1) were significantly increased, suggesting a polarization towards the Mox phenotype after α 7R stimulation. Thus, our data suggest a role for the α 7R also in the neonatal brain and support the anti-inflammatory role of α 7R in microglia, suggesting that α 7R stimulation could enhance the polarization towards a reparative Mox phenotype.
Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
Sansan
S
Hua
Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
C Joakim
CJ
Ek
Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
Carina
C
Mallard
Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
Maria E
ME
Johansson
D000818:Animals; D000831:Animals, Newborn; D051940:B7-2 Antigen / Q000096:biosynthesis; D005786:Gene Expression Regulation; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type / Q000096:biosynthesis; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000096:biosynthesis*
D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D064569:alpha7 Nicotinic Acetylcholine Receptor; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse