Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

L. Conboy, E. Varea, J. E. Castro, H. Sakouhi-Ouertatani, T. Calandra, H. A. Lashuel, C. Sandi

Research output: Contribution to journalArticle

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Abstract

Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1) approaches. Behaviorally, genetic deletion of MIF resulted in increased anxiety- and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Together, our studies provide evidence supporting a pivotal function for MIF in both basal and antidepressant-stimulated adult hippocampal cell proliferation. Moreover, loss of MIF results in a behavioral phenotype that, to a large extent, corresponds with alterations predicted to arise from reduced hippocampal neurogenesis. These findings underscore MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition.

Original languageEnglish
Pages (from-to)533-547
Number of pages15
JournalMolecular Psychiatry
Volume16
Issue number5
DOIs
Publication statusPublished - 1 May 2011
Externally publishedYes

Fingerprint

Macrophage Migration-Inhibitory Factors
Fluoxetine
Neurogenesis
Anxiety
Cell Proliferation
Depression
Antidepressive Agents
Dentate Gyrus
Gene Deletion
Cognition
Rodentia
Hippocampus
Stem Cells
Pharmacology
Cytokines
Phenotype
Research

Keywords

  • anxiety
  • depression
  • fluoxetine
  • memory
  • MIF
  • neurogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors. / Conboy, L.; Varea, E.; Castro, J. E.; Sakouhi-Ouertatani, H.; Calandra, T.; Lashuel, H. A.; Sandi, C.

In: Molecular Psychiatry, Vol. 16, No. 5, 01.05.2011, p. 533-547.

Research output: Contribution to journalArticle

Conboy, L. ; Varea, E. ; Castro, J. E. ; Sakouhi-Ouertatani, H. ; Calandra, T. ; Lashuel, H. A. ; Sandi, C. / Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors. In: Molecular Psychiatry. 2011 ; Vol. 16, No. 5. pp. 533-547.
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