Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors
| Autor: | Carmen Sandi, Hajer Sakouhi-Ouertatani, Lisa Conboy, Emilio Varea, Jorge E. Castro, Hilal A. Lashuel, Thierry Calandra |
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| Předmět: |
Receptors
Steroid Stem-Cells animal diseases medicine.medical_treatment Hippocampus Expression Hippocampal formation Subgranular zone memory Mice 0302 clinical medicine Conditioning Psychological Cyclin D2 Rat Dentate Gyrus Mice Knockout Neurons 0303 health sciences Microscopy Confocal Chronic Stress Mif Neurogenesis Brain Fear respiratory system anxiety Psychiatry and Mental health C-Reactive Protein Cytokine medicine.anatomical_structure depression Antidepressive Agents Second-Generation Stem cell Psychology Animal-Model Spatial Behavior Nerve Tissue Proteins chemical and pharmacologic phenomena 03 medical and health sciences Cellular and Molecular Neuroscience medicine otorhinolaryngologic diseases Animals Rats Wistar Maze Learning Macrophage Migration-Inhibitory Factors Molecular Biology Cell Proliferation 030304 developmental biology Memory Disorders Dentate gyrus fluoxetine Factor Mif biological factors Rats Disease Models Animal Acoustic Stimulation Bromodeoxyuridine Macrophage migration inhibitory factor Corticosterone Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecular psychiatry Molecular Psychiatry; Vol 16 |
| Popis: | 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.Molecular Psychiatry advance online publication, 23 February 2010; doi:10.1038/mp.2010.15. |
| Databáze: | OpenAIRE |
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