title: Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via PI3K/Akt Activation and Bcl-2 Expression.
abstract: Olfactory stimulation activates multiple signaling cascades in order to mediate activity-driven changes in gene expression that promote neuronal survival. To date, the mechanisms involved in activity-dependent olfactory neuronal survival have yet to be fully elucidated. In the current study, we observed that olfactory sensory stimulation, which caused neuronal activation, promoted activation of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and the expression of Bcl-2, which were responsible for olfactory receptor neuron (ORN) survival. We demonstrated that Bcl-2 expression increased after odorant stimulation both in vivo and in vitro. We also showed that odorant stimulation activated Akt, and that Akt activation was completely blocked by incubation with both a PI3K inhibitor (LY294002) and Akt1 small interfering RNA. Moreover, blocking the PI3K/Akt pathway diminished the odorant-induced Bcl-2 expression, as well as the effects on odorant-induced ORN survival. A temporal difference was noted between the activation of Akt1 and the expression of Bcl-2 following odorant stimulation. Blocking the PI3K/Akt pathway did not affect ORN survival in the time range prior to the increase in Bcl-2 expression, implying that these two events, activation of the PI3K pathway and Bcl-2 induction, were tightly connected to promote post-translational ORN survival. Collectively, our results indicated that olfactory activity activated PI3K/Akt, induced Bcl-2, and promoted long term ORN survival as a result.
authors.affiliation: Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea.
authors.forename: So Yeun
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea.
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Yoo
authors.affiliation: Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea.|Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.|Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Ronnett
authors.affiliation: Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Brain & Cognitive Sciences, Graduate School Daegu Gyeungbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea.
authors.forename: Cheil
authors.initials: C
authors.lastname: Moon
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Bcl-2; PI3K/Akt; odorant; olfactory receptor neuron; survival