Leukemia inhibitory factor promotes olfactory sensory neuronal survival via phosphoinositide 3-kinase pathway activation and Bcl-2

Cheil Moon, Bridget Q. Liu, So Yeun Kim, Esther J. Kim, Yun Ju Park, Joo Yeon Yoo, Hyung Soo Han, Yong Chul Bae, Gabriele V. Ronnett

Research output: Contribution to journalArticlepeer-review

Abstract

Leukemia inhibitory factor (LIF), a neuropoietic cytokine, has been implicated in the control of neuronal development. We previously reported that LIF plays a critical role in regulating the terminal differentiation of olfactory sensory neurons (OSNs). Here, we demonstrate that LIF plays a complementary role in supporting the survival of immature OSNs. Mature OSNs express LIF, which may be elaborated in a paracrine manner to influence adjacent neurons. LIF null mice display more apoptotic immature neurons than do their wild-type littermates. LIF treatment of dissociated OSNs in vitro significantly reduces the apoptosis of immature OSNs. Double immunocytochemical analysis indicates that the survival of immature OSNs is dependent on the presence of LIF. LIF activates the phosphoinositide 3-kinase (PI3K) pathways and induces the expression of the antiapoptotic molecule Bcl-2 in OSNs, whereas inhibition of the PI3K pathway blocks LIF-dependent OSN survival and Bcl-2 induction. Thus, LIF plays a central role in maintaining the size and integrity of the population of immature neurons within the olfactory epithelium; this population is critical to the rapid recovery of olfactory function after injury. LIF may play a similar role elsewhere in the CNS and thus be important for manipulation of stem cell populations for therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)1098-1106
Number of pages9
JournalJournal of Neuroscience Research
Volume87
Issue number5
DOIs
StatePublished - 2009

Keywords

  • Bcl-2
  • Development
  • Leukemia inhibitory factor
  • Maturation
  • Olfactory sensory neuron
  • Phosphoinositide 3-kinase
  • Terminal differentiation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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