Odorant-Induced Activation of Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase in the Olfactory Bulb Promotes Survival of Newly Formed Granule Cells

Abstract

Extracellular signal-regulated kinase 1/2 (Erk1/2)/mitogen-activated protein (MAP) kinase (MAPK) plays a significant role in neuronal survival, including odorant-induced, activity-dependent survival of olfactory sensory neurons in the main olfactory epithelium. Here, we examined the role of MAPK for the survival of neurons in the olfactory bulb. To study odorant-induced activation of MAPK in the olfactory bulb, mice were exposed to odorants in vivo, and MAPK was assayed. Exposure of mice to some odorants in vivo activated MAPK in granule cells 10 min after exposure. Activation of MAPK was particularly evident in the nucleus and dendrites of granule cells. Because MAPK activation can augment neuronal survival, odorant enhancement of granule cell survival was monitored by bromodeoxyuridine (BrdU) incorporation. Long-term exposure to odorants increased the survival of newly formed granule cells as well as the number of granule cells that were both BrdU+ and phospho-Erk+. Inhibition of MAPK by administration of SL327 in vivo blocked the odorant-induced increase in newly formed granule cells, suggesting that activation of MAPK promotes the survival of granule cells in the olfactory bulb. Studies using cultured granule cells confirmed that activation of MAPK in granule cells protects them against strong apoptotic signals. These data suggest that stimulation of MAPK in olfactory bulb granule cells by some odorants may contribute to the survival of newly formed granule cells caused by odorant exposure.